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Understanding the Mechanisms: A Comprehensive Analysis of Dr. Rhonda Patrick's Insights on Vigorous Exercise and its Impact on Longevity and Brain Health

In this analysis, Shreshtha Jolly from the Johns Hopkins Department of Molecular Biology provides a scientific exploration into the myriad benefits of vigorous exercise as highlighted in Dr. Rhonda Patrick's podcast "The Longevity & Brain Benefits of Vigorous Exercise." The article delves into the molecular and physiological impacts of High-Intensity Interval Training (HIIT), focusing on its profound influence on heart and brain health, cancer prevention, and the aging process. This comprehensive review aims to elucidate the significant role of vigorous exercise in enhancing overall well-being, marrying Dr. Patrick's expertise with cutting-edge research in the field.

Cognitive Health

Neurological Health



cancer prevention

Dr. Rhonda Patrick


32 mins

By: Shreshtha Jolly, Daniel Tawfik

A recent podcast by Dr. Rhonda Patrick, titled “The Longevity & Brain Benefits of Vigorous Exercise”, has shed light on the numerous advantages of high-intensity vigorous exercise. Dr. Patrick, renowned for her extensive research in the fields of nutrition, aging, and fitness, discusses how vigorous exercise not only improves physical health but also has profound impacts on brain function.

In this article, Shreshtha Jolly, from the Johns Hopkins Department of Molecular Biology, will delve deeper into the insights provided by Dr. Patrick, complementing them with related research to fully grasp the significance of vigorous exercise in enhancing longevity and brain health. Jolly will elaborate on the molecular underpinnings of vigorous exercise, particularly emphasizing High-Intensity Interval Training (HIIT).

In this exploration, we'll cover the profound effects of vigorous exercise on heart and brain health, its potential role in cancer prevention and management, and its influence on the aging process. By integrating these perspectives, we aim to provide a well-rounded view of the transformative power of high-intensity, vigorous exercise on overall well-being.

What is vigorous exercise?

Vigorous exercise encompasses physically demanding activities of high intensity that significantly elevate heart rate and energy expenditure. According to the American Heart Association (AHA), exercise falls into the "vigorous" category if it causes your heart to beat at 70% to 85% of your maximum heart rate. One way to assess whether you are exercising vigorously is through the word test. If a person exercises vigorously, they cannot speak more than a few words at a time without taking a breath.

The intensive nature of vigorous exercises yields numerous health benefits. Recognizing these advantages, public health agencies advocate for adults to engage in at least 75 minutes of vigorous exercise per week. This recommendation underscores the importance of incorporating such activities into one's routine for optimal health and well-being. [1] In fact, according to Dr. Rhonda Patrick, casual exercisers (engage in physical activity 2-3 times a week) and committed exercisers (engage in physical activity 3-5 times a week) should devote half of their weekly exercise time to vigorous-intensity exercise. [2]

Various forms of activity can constitute vigorous exercises. Some examples of these include:

  • Hiking uphill or with a heavy backpack

  • Running

  • Swimming laps

  • Aerobic dancing

  • Tennis (singles)

  • Cycling at a rate of 10 or more miles per hour

  • Heavy yard work like continuous digging or hoeing

  • Jumping rope

These exercises can cause your heart to beat at 70 to 85% of your maximum heart rate. They are thus considered vigorous. Apart from heartbeat, a second parameter commonly used to measure exercise intensity is metabolic equivalents (METs). METs gauge the intensity of physical activity by measuring the amount of oxygen a person consumes at rest. For instance, an activity with a rating of 2 METs means a person uses twice the amount of oxygen they would use at rest. All above-reported exercises are characterized by a MET rating of 6 or more, deeming them highly intensive or vigorous. [3]

Understanding Aerobic and Anaerobic Energy Systems in Exercise: The Key to Endurance and Power

The energy systems needed to propel your muscles during various forms of exercise are critical to understanding the longevity benefits of exercise. Your muscles use different systems to get the energy they need. The two fundamental types of energy systems are aerobic and anaerobic.

The aerobic energy system, fundamentally, is the primary energy pathway used by the body during prolonged, low to moderate intensity activities. This system's efficiency lies in its ability to utilize oxygen for the breakdown of nutrients, primarily carbohydrates and fats, to generate adenosine triphosphate (ATP) – the molecular unit of currency for energy within the body.

During aerobic activities such as long-distance running or cycling, the body relies on this system for its ability to produce a large amount of ATP over a longer period. This is opposed to anaerobic systems, which generate energy quickly but in limited amounts and for shorter durations, often resulting in the production of lactate and a quicker onset of fatigue.

What distinguishes the aerobic system is its reliance on the circulatory system to deliver oxygen to the muscles. The more efficiently the heart and lungs work to transport oxygen, the more effectively this system functions. This efficiency is why endurance training can lead to physiological adaptations like increased stroke volume of the heart and enhanced oxygen uptake in muscles, both crucial for improving endurance performance.

Furthermore, the choice between carbohydrates and fats as fuel depends on various factors, including the intensity and duration of the activity, and the individual's diet and fitness level. Typically, during lower-intensity activities, the body tends to utilize a higher proportion of fat for energy, whereas for higher intensity activities, the reliance shifts more towards carbohydrates.

In essence, the aerobic energy system is a complex but highly efficient system, integral for sustained physical activities. Its reliance on oxygen, ability to use different fuel sources, and adaptability through training, make it fundamental for endurance sports and activities.

On the other hand, the anaerobic system is more like a sprinter's burst of energy. It is the system your body uses when you need a quick burst of power for short and intense activities, like sprinting or lifting something heavy. This system does not rely on oxygen; instead, it quickly breaks down sugars stored in your muscles to produce energy. It is powerful but gets exhausted faster than the aerobic system. [4]

So, depending on the type of exercise you're doing—whether it is a slow, steady activity like jogging or a quick, intense activity like sprinting—your body will use either the aerobic or anaerobic system.

One form of vigorous physical activity that manages to engage both types of energy systems is high-intensity interval training (HIIT). In this type of training, individuals alternate between periods of high-intensity exercise and intervals of lower-intensity exercise or rest. The ability of HIIT to incorporate both systems makes it a powerful tool to enhance one's overall fitness levels. [2]

HIIT and VO2 Max Enhancement: Maximizing Cardiovascular Fitness and Longevity

Besides engaging both energy systems, HIIT's added benefit is its ability to enhance the VO2 max. VO2 max, or maximal oxygen uptake, is the maximum rate at which the body can use oxygen during intense exercise. It's widely considered the gold standard for measuring cardiorespiratory fitness and aerobic endurance. Higher VO2 max levels correlate strongly with improved health and extended lifespan.

Research indicates that incremental improvements in VO2 max can have profound health benefits. A study by Kokkinos et al. (2010) found that each 1 MET (metabolic equivalent) increase in VO2 max (roughly equivalent to a 3.5 ml/kg/min increase) was associated with a 13% decrease in mortality risk [6]. This is particularly significant for individuals starting at below-average fitness levels, as they often observe the most dramatic improvements with consistent exercise like HIIT.

Given the importance of VO2 max in longevity, the question that arises is, are there ways to measure it? Measuring VO2 max without specialized exercise lab equipment is challenging, but there are validated tests that estimate it indirectly based on how your body responds during exercise.

One popular test is the 12-minute run or walk, also known as the Cooper test, as recommended by Dr. Rhonda Patrick. For this test, you run or walk as far as possible in 12 minutes, pacing yourself evenly. Doing this on a flat surface like a track field is best. Using a fitness device like an Apple Watch or Fitbit to track the distance you have covered is helpful. The distance you cover in those 12 minutes is then used in a formula to estimate your VO2 max. [2]

Metabolic Advantages of HIIT: Enhancing Glucose Control and Insulin Sensitivity for Better Health

In addition to engaging both energy systems and enhancing one's VO2 max, HIIT also instills metabolic benefits in an individual. HIIT's effectiveness in improving glucose control and insulin sensitivity is indeed a significant aspect of its metabolic benefits.

Insulin sensitivity refers to how sensitive the body's cells are to insulin. Higher insulin sensitivity allows the cells to use blood glucose more effectively, reducing blood sugar levels. Conversely, reduced insulin sensitivity, or insulin resistance, is a major risk factor for type 2 diabetes and other metabolic disorders.

The unique metabolic stress induced by HIIT is key to its benefits. During high-intensity bouts, the body's demand for energy surges, leading to rapid glucose uptake from the blood into the muscles. In order to transport glucose into the cell, glucose transporters, primarily GLUT4, move to the cell surface in response to muscle contractions and insulin [7]. This increased activity of glucose transporters enhances muscle cells' ability to absorb glucose, thereby improving blood sugar control.

A study by Boutcher (2011) highlights that HIIT leads to significant improvements in glucose control and insulin sensitivity in both diabetic and non-diabetic individuals compared to moderate-intensity continuous training (MICT) [8]. This is attributed to the intense, intermittent nature of HIIT, which provides a more robust stimulus for improving metabolic functions than steady-state, moderate exercise. This includes more significant increases in heart rate and muscle activation, leading to greater adaptations in the cardiovascular system and muscle tissue. These adaptations may improve the muscles' ability to use glucose and respond to insulin. As we will see later, modifying the levels of insulin and available glucose has a profound effect on overall longevity.

Additionally, HIIT's ability to improve glucose metabolism extends beyond the period of exercise itself. The afterburn effect, or excess post-exercise oxygen consumption (EPOC), where the body continues to burn calories at an elevated rate post-exercise, is higher following HIIT sessions compared to moderate-intensity exercise [9]. This extended metabolic activity further contributes to improved glucose regulation and overall metabolic health.

The total metabolic benefits of HIIT, particularly in terms of glucose control and insulin sensitivity, are substantial. By inducing intense metabolic stress, HIIT activates glucose transporters more effectively than moderate-intensity exercise, leading to enhanced glucose uptake by muscles and improved overall metabolic health. These effects are beneficial not just for individuals with existing metabolic disorders, but also for those looking to improve their metabolic health proactively.

Revitalizing Cellular Powerhouses: How HIIT Boosts Mitochondrial Health and Metabolic Efficiency

HIIT also plays a crucial role in mitochondrial health. Mitochondria, often described as the powerhouses of the cell, are responsible for producing the energy (ATP) needed for various cellular functions. It's well-established that mitochondrial efficiency declines with age, leading to decreased energy production and increased susceptibility to diseases [10]. However, exercise, particularly HIIT, has been shown to counteract this decline by stimulating mitochondrial biogenesis, which is the creation of new mitochondria [11].

The process of mitochondrial biogenesis induced by HIIT is significant because it not only increases the number of mitochondria but also enhances their function. This is crucial for maintaining the health and efficiency of tissues, particularly those with high energy demands like the heart and muscles. Furthermore, improved mitochondrial function supports overall metabolic health, contributing to better organ function and potentially delaying the onset of age-related decline.

HIIT’s impact on mitochondrial health also enhance our ability to burn fat as an energy source. The enhancement of specific proteins like Carnitine Palmitoyltransferase (CPT), which is pivotal in transporting fatty acids into mitochondria for oxidation (i.e., burning), is a key factor here. This process allows for more efficient fat breakdown and usage as a fuel source during exercise [12].

The improved mitochondrial function resulting from HIIT leads to more efficient fat breakdown during exercise. This means that during periods of physical activity, the body can more effectively tap into fat stores for energy, which is particularly beneficial for endurance and performance, as well as for overall energy balance and weight management.

The term "strong metabolic engine" refers to the body's metabolic flexibility, or its ability to efficiently switch between different fuel sources (like carbohydrates and fats) based on availability and demand. An optimized metabolic engine is efficient in using both glucose and fat as energy sources. This flexibility is beneficial not just for athletic performance but also for overall metabolic health, as it can lead to improved energy regulation and reduced risk of metabolic disorders.

Exercise and Mitophagy

Dr. Rhonda Patrick's emphasis on mitophagy in relation to HIIT is another critical aspect of the mitochondrial adaptions to exercise. Mitophagy is a selective form of autophagy where damaged or dysfunctional mitochondria are removed and recycled. This process is essential for maintaining mitochondrial quality and preventing the accumulation of defective mitochondria, which can lead to cellular dysfunction and disease [13]. While research on mitophagy in response to different types of exercise, particularly in humans, is still emerging, HIIT has been shown to stimulate factors involved in this process, thereby contributing to the maintenance of a healthy mitochondrial network.

In total, HIIT plays a multifaceted role in enhancing mitochondrial health by stimulating the production of new mitochondria, improving mitochondrial function, and facilitating the removal of damaged mitochondria. These benefits extend beyond simply increasing energy production; they have profound implications for overall metabolic health, fat metabolism, and potentially slowing down age-related decline in organ function.

The Effects of HIIT Exercise Training and Brain Health: The Surprising Role of Lactate in Neuronal Energy and Neurogenesis

In her podcast, Dr. Rhonda Patrick also alerts us to the importance of HIIT in brain health. During HIIT, the body's demand for energy exceeds the oxygen supply, leading to anaerobic metabolism where glucose is converted into lactate. We’ve all experienced the symptoms of this lactate buildup in the form of muscle fatigue and soreness. However, this lactate, contrary to previous beliefs, is not merely a waste product—it’s an actual fuel source. The lactate produced during high-intensity exercise is released into the bloodstream and is available for use by various organs, including the brain. It can be taken up by different tissues, including muscle cells, and converted back into energy

Lactate travels through the bloodstream and crosses the blood-brain barrier, a selective permeable barrier that regulates the passage of substances into the brain. Once in the brain, lactate is utilized by neurons for energy. Research indicates that neurons can metabolize lactate efficiently, sometimes even preferring it over glucose, their usual energy source [14].

Neurons have high energy demands, and the efficient delivery of energy is crucial for their function. The use of lactate as an alternative energy source can be particularly important under conditions where glucose is less available or during intense neuronal activity. The ability of neurons to switch between glucose and lactate for energy reflects the metabolic flexibility of the brain.

Lactate's role in the brain extends beyond being an alternative fuel source. It plays a critical part in conserving glucose for other essential brain functions. Glucose in the brain is not only used for energy but also for synthesizing neurotransmitters and maintaining the myelin sheath surrounding neurons. By utilizing lactate as an alternative fuel, neurons can spare glucose for these critical processes.

Furthermore, lactate influences the release of neurotransmitters, the chemical messengers that facilitate communication between neurons. This process is akin to a river channel facilitating the transport of cargo; neurotransmitters help transmit signals across synapses from one neuron to another, ensuring efficient neural communication.

Another significant aspect of lactate's role in brain health is its impact on Brain-Derived Neurotrophic Factor (BDNF). BDNF is a member of the neurotrophin family of growth factors, which are essential for the development, survival, and plasticity of neurons in the brain. It plays a crucial role in learning and memory by supporting the growth and differentiation of new neurons and the maintenance of existing ones. BDNF is also involved in synaptic plasticity, which is the ability of synapses (the points of communication between neurons) to strengthen or weaken over time. This plasticity is crucial for learning and memory formation.

Increased levels of BDNF, stimulated by exercise-induced lactate, contribute to neurogenesis, which is the formation of new neurons in the brain. This process is particularly active in the hippocampus, an area of the brain critical for memory and learning. By promoting neurogenesis and enhancing brain plasticity, exercise can contribute to improved cognitive abilities, memory, and potentially a lower risk of neurodegenerative diseases. Moreover, these effects underscore the importance of regular physical activity for maintaining and improving brain health [15].

Lastly, lactate is involved in promoting angiogenesis, the formation of new blood vessels in the brain. This process is vital for maintaining adequate blood flow, providing nutrients and oxygen, and facilitating repair mechanisms within the brain. The ability of lactate to promote angiogenesis has significant implications for brain health. Enhanced angiogenesis can improve cerebral blood flow, thereby potentially improving cognitive function and brain resilience. This is particularly relevant in situations of increased metabolic demand, such as during intense cognitive tasks, or in recovery and repair processes following injury or in neurodegenerative diseases [16].

Vigorous Exercise: A Multifaceted Protector Against Heart Disease and a Potent Rejuvenator of Cardiac Health

As we’re establishing, there exist numerous benefits of vigorous exercise. For instance, setting aside 15 minutes per week for vigorous exercise can lower your risk of heart disease, cancer, and even early death. This finding comes from a study published by the European Heart Journal. In the study, researchers observed nearly 72,000 adults with an average age of 62, all of whom were initially free of cardiovascular disease or cancer.

Throughout the study, participants wore wrist activity trackers. The tracker measured their overall activity levels, including vigorous activity levels and their frequency. After a follow-up period of seven years, astonishingly, the study found that dedicating as little as 15 minutes per week to vigorous exercise was associated with an 18% decrease in mortality risk. Moreover, engaging in 19 minutes of vigorous exercise showcased a 40% reduction in the chances of developing heart disease, while committing to 16 minutes correlated with a 16% decrease in cancer risk. [2]

Vigorous exercise, when performed consistently, also helps reduce a condition known as coronary heart disease (CHD). This condition is characterized by plaque accumulation within the coronary arteries. The coronary arteries are blood vessels that help supply oxygen-rich blood to the heart muscle. When plaque builds up in these blood vessels, it causes the arteries to narrow.

Narrowed arteries greatly diminish blood flow to the heart. To make matters worse, sometimes the plaque can rupture, resulting in blood clots on its surface. These clots can then entirely block blood flow through a coronary artery, resulting in what is commonly known as a heart attack.

When performed consistently, it turns out vigorous physical activity can help manage the risk factors that are otherwise associated with CHD. Typically, CHD arises because of:

  • High blood pressure and levels of triglycerides (a type of blood fat)

  • Low levels of high-density lipoproteins (HDLs). Think of HDLs as responsible cleaning trucks in your body. They pick up excess cholesterol from different areas, clean up the streets (blood vessels), and return the cholesterol to the liver for recycling. 

  • Obesity 

  • Increased levels of C-reactive protein (CRP). Think of CRP as a security system in your body. It helps respond to signs of inflammation and helps coordinate the immune system's response to keep everything in order. 

  • Smoking

However, we know that vigorous exercise, in particular, targets these pathways.

High Blood Pressure and Triglyceride Levels: Vigorous exercise is known to have a beneficial effect on both blood pressure and triglycerides. Regular intense physical activity strengthens the heart muscle, improving its efficiency in pumping blood, which can lower blood pressure. Additionally, exercise helps in the enzymatic regulation of triglyceride metabolism, leading to reduced blood triglyceride levels. A foundational study by Kraus et al. published in the New England Journal of Medicine showed that high-intensity physical activity significantly reduces triglyceride levels while improving other lipid profiles [17].

Low Levels of High-Density Lipoproteins (HDLs): HDL cholesterol, often referred to as 'good' cholesterol, plays a crucial role in reversing cholesterol transport. It helps in transporting cholesterol from other parts of the body back to the liver, where it can be removed or reused. Vigorous exercise has been shown to increase HDL levels, thus enhancing this protective mechanism against heart disease [18].

Lowering Levels of C-Reactive Protein (CRP): CRP is an inflammatory marker, and high levels are associated with an increased risk of heart diseases. Exercise has an anti-inflammatory effect on the body, which includes reducing CRP levels. Regular vigorous exercise can lower inflammation, partially mediated through weight loss, but also through other mechanisms independent of weight loss [19].

Smoking: While exercise itself doesn't directly affect smoking habits, adopting a regular exercise routine can be a part of a healthier lifestyle that may encourage smoking cessation. Additionally, for those who have quit smoking, exercise can mitigate some of the weight gain commonly associated with quitting and help in managing stress and withdrawal symptoms.

Exercise and Heart Aging

Besides counteracting CHD, vigorous physical exercise also reverses heart aging. Aging is associated with several changes in the heart, including a decrease in the size of the heart muscle, increased stiffness of the heart chambers (particularly the left ventricle), and reduced efficiency in pumping blood. These changes can lead to various cardiac issues, including an increased risk of heart failure and other heart diseases.

However, consistent aerobic exercise, particularly at high intensities, has been shown to counteract these age-related changes. The mechanisms through which vigorous exercise achieves this are multifaceted:

1. Improved Cardiac Plasticity

Vigorous exercise enhances the heart's plasticity, which refers to its ability to adapt and remodel itself in response to increased physical demands. This includes increasing the size of the heart chambers, improving the heart muscle's ability to contract, and reducing stiffness in the heart walls [20].

A study titled "Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial: Implications For Heart Failure Prevention" focused on examining the effects of two years of supervised high-intensity exercise training on left ventricular (LV) stiffness in middle-aged adults. The study involved 61 healthy, sedentary, middle-aged individuals (53±5 years old), with nearly equal male and female representation. Participants were randomly assigned to either a two-year exercise training regimen or an attention control group. The exercise training included high-intensity sessions, designed to progressively challenge the participants and improve their cardiovascular fitness.

The study had three key findings:

Increased Maximal Oxygen Uptake: Participants in the exercise training group showed an 18% increase in maximal oxygen uptake, indicating improved fitness.

Reduced LV Stiffness: There was a significant reduction in left ventricular stiffness in the exercise group, suggesting improved cardiac health and function.

Enhanced Cardiac Volumes: Exercise led to increased left ventricular end-diastolic volume, allowing for greater stroke volume without increasing filling pressure. The study concluded that regular exercise training in previously sedentary, healthy middle-aged adults improved maximal oxygen uptake and decreased cardiac stiffness, potentially offering protection against heart failure with a preserved ejection fraction related to sedentary aging​​.

The study showed that two years of vigorous exercise could reverse heart aging by up to 20 years, highlights these effects [20]. This research suggests that not only can exercise prevent heart aging, but it can also reverse some of the age-related changes that have already occurred.

2. Enhanced Blood Flow and Oxygen Delivery

Regular high-intensity exercise improves the heart's pumping capacity, which enhances blood flow and oxygen delivery to tissues. This increased efficiency can help to maintain the health of the heart muscle and delay the onset of age-related decline [20].

3. Molecular and Cellular Adaptations

Exercise induces molecular and cellular adaptations in the heart. These adaptations include changes in the expression of genes and proteins that are involved in maintaining the structure and function of cardiac cells, combating oxidative stress, and improving metabolic processes within the heart [21].

Conclusively, vigorous physical exercise emerges as a means to counteract the risks associated with CHD and as a potent elixir for rejuvenating the heart. Its multifaceted impact, from curbing risk factors like high blood pressure, elevated lipids, obesity, and inflammation to potentially aiding in smoking cessation, underscores its pivotal role in cardiac health. Moreover, the remarkable reversal of heart aging observed in studies amplifies the transformative power of regular, vigorous exercise.

How Vigorous Activity Lowers Cancer Risk Through Improved Metabolism and Hormone Regulation

Vigorous exercise isn't just good for your muscles and heart but it’s a powerful tool against certain types of cancer. While scientists have not nailed down a direct cause-and-effect relationship, it turns out that tweaking your lifestyle to incorporate vigorous exercise has powerful anti-cancer benefits.

Engaging in moderate exercise for 3 to 5 hours per week can significantly slash your risk of various cancers. For instance, engaging in energetic dance sessions or heavy housework can lower the risk of breast cancer by 15% to 20%. Furthermore, engaging in regular exercise can help drop colorectal cancer risk by a whopping 24%. Besides this, incidences of esophageal, kidney, stomach, and endometrial cancer are also lower with vigorous physical exercise.

How does vigorous exercise decrease cancer? It turns out that vigorous physical exercise can help by:

1. Improving Blood Flow

Several physiological processes at play underlie cancer development. One specific mechanism involves tumor cells escaping the original site, entering circulation, and forming tumors at other locations in the body (secondary tumors). This process is known as cancer metastasis. These circulating tumor cells are now sensitive to the shearing forces of blood flow. Intense and prolonged exercise can improve blood flow and induce the death of tumor cells, thus reducing the incidence of secondary tumor formation. It is as if they trigger a tsunami that wipes everything.

2. Lowering Levels of Certain Hormones Like Estrogen

Heightened levels of estrogen and testosterone are often associated with the progression of certain types of cancers, such as breast and colon cancer. Exercise influences hormone levels through several mechanisms. These include changes in body composition (as both fat and muscle can influence hormone production and metabolism), alterations in the metabolic clearance rate of hormones, and changes in the production of hormone-binding proteins.

3. Curbing Elevated Insulin Levels

Insulin is a crucial hormone for regulating blood glucose levels. After eating, blood glucose levels rise, prompting the pancreas to release insulin. Insulin facilitates the uptake of glucose into cells, where it's used for energy, effectively lowering blood glucose levels. Insulin's role is akin to a delivery person, as mentioned, ensuring that glucose is distributed to cells throughout the body.

Elevated insulin levels, a condition known as hyperinsulinemia, can have several adverse effects on the body, including contributing to cancer risk. High levels of insulin can increase the production of Insulin-like Growth Factor 1 (IGF-1). IGF-1 is a hormone that plays a key role in cell growth and development. While normal levels of IGF-1 are essential for healthy growth, excessive IGF-1 can lead to abnormal growth processes [22].

IGF-1 promotes cell proliferation and inhibits apoptosis (programmed cell death), which are both crucial processes in cancer development. Increased cell proliferation combined with a decreased rate of cell death can lead to an accumulation of mutations and an increased likelihood of cancerous growths [23]. High levels of IGF-1 have been linked to several types of cancer, including breast, prostate, and colorectal cancers.

Regular physical exercise, including vigorous activities, is known to improve insulin sensitivity. Improved insulin sensitivity means that the body requires less insulin to lower blood glucose levels, thereby reducing the risk of hyperinsulinemia. This, in turn, can lead to lower levels of circulating IGF-1, potentially reducing the risk of cancer development associated with high IGF-1 levels [24].

4. Lowering Inflammation

Cytokines are small proteins released by cells, especially immune cells, that play a crucial role in cell signaling, particularly during immune responses to injury or infection. They can be pro-inflammatory or anti-inflammatory, helping to start, sustain, or resolve inflammatory processes. However, chronic elevated levels of certain pro-inflammatory cytokines can lead to persistent inflammation, which is a known risk factor for several diseases, including cancer [25].

Regular vigorous exercise is known to modulate the production of cytokines. During exercise, muscles release a group of cytokines known as myokines, which have anti-inflammatory effects. One well-studied myokine is interleukin-6 (IL-6), which increases during muscle contraction and has both pro- and anti-inflammatory effects. However, in the context of exercise, IL-6 tends to exert anti-inflammatory actions by stimulating the production of other anti-inflammatory cytokines and inhibiting the release of pro-inflammatory cytokines [26].

Chronic inflammation is a state where inflammatory processes in the body are persistently activated, often due to conditions like obesity, stress, or persistent infections. This state is linked to increased cancer risk because it can lead to DNA damage, promote angiogenesis (the formation of new blood vessels that can feed tumors), and support the survival and proliferation of malignant cells [27]. By lowering the levels of pro-inflammatory cytokines and promoting anti-inflammatory pathways, vigorous exercise can reduce the risk of chronic inflammation.

The reduction in chronic inflammation through regular vigorous exercise can subsequently lower the risk of cancer development. The anti-inflammatory effects of exercise help in mitigating the pro-tumorigenic environment created by chronic inflammation, thereby playing a protective role against the initiation and progression of various cancers [28].

5. Boosting the Immune System

Vigorous physical exercise has a profound impact on the immune system. It stimulates the production and circulation of immune cells, like natural killer (NK) cells, neutrophils, and T cells. These cells play a critical role in identifying and eliminating pathogens and abnormal cells, including those that could potentially develop into cancer [29].

NK cells, a type of lymphocyte, are particularly important in the context of cancer prevention. They have the ability to recognize and destroy cells that are stressed or altered, such as cancerous or pre-cancerous cells, without the need for prior sensitization to specific antigens. Exercise has been shown to increase the activity and circulation of NK cells, enhancing the body's surveillance against cancerous cells [30].

While acute vigorous exercise can cause a temporary increase in immune cell function, regular, chronic exercise leads to long-term improvements in immune surveillance. This is important for cancer prevention as it enhances the body’s ability to detect and eliminate abnormal cells before they can convert into tumors [31].

As previously discussed, exercise reduces chronic inflammation, which is beneficial for immune function. Chronic inflammation can suppress immune surveillance and create an environment conducive to cancer development. By reducing inflammation, exercise helps maintain an effective immune response against potential cancer cells [32].

Stress Reduction and Immune Function: Vigorous exercise is also known to reduce stress and anxiety, which can positively affect the immune system. Chronic stress can suppress immune function, including the activity of NK cells. Exercise-induced stress reduction may therefore contribute to enhanced immune surveillance and cancer prevention [33].

Physical activity also influences how our bodies process bile acids. Think of bile acids as your body's soap for digestion. When you eat, especially fatty foods, your body needs help breaking them down. That's where bile acids come in. These acids are made in your liver and stored in your gallbladder. When you eat, your gallbladder releases these acids into your intestines. Their job is to break down fats from the food you've eaten into smaller pieces so your body can absorb them better, like how soap helps clean oily dishes. Regular vigorous exercise can alter bile acid metabolism by reducing the concentration of potentially harmful bile acids in the gastrointestinal tract. This then lowers the risk of developing colon cancer.

Regular physical exercise also improves and speeds up your digestion. This reduces the time for possible carcinogens to stay in the digestive system, further lowering risks associated with colon cancer.

Overall, vigorous exercise emerges as an unexpected ally in the battle against cancer, showcasing its potential to significantly reduce the risk of various types of this debilitating disease. The intricate mechanisms through which vigorous physical activity exerts its protective effects are multifaceted and compelling. Its impact on lowering cancer risk is profound, from enhancing blood flow and potentially preventing the spread of tumor cells to modulating hormone levels and curbing inflammation. Additionally, the influence on immune function, bile acid metabolism, and digestion further fortifies the case for incorporating vigorous exercise into one's lifestyle.

How Vigorous Activity Combats Aging by Repairing DNA Damage

Vigorous exercise promotes longevity by reducing incidences of cancer and chronic cardiovascular conditions. It also promotes longevity by mediating anti-aging effects. It accomplishes this by two mechanisms - (a) reversing existing signs of aging and/or (b) delaying their manifestation.

One way by which it accomplishes this is through repair. As we get older, our body changes, like how cars develop wear and tear over time. These changes occur in the DNA. Many of these changes are triggered by reactive oxygen species (ROS). ROS are highly reactive molecules containing oxygen naturally produced in our bodies when our cells use oxygen to produce energy. They can damage DNA by oxidizing it, meaning they steal electrons (or negative charges) from the DNA molecules. This theft of electrons can cause breaks or lesions in the DNA structure.

Apart from oxidation, they may also react directly with the DNA, altering its sequence or impairing its capacity to replicate accurately. Finally, they may also contribute to DNA damage by triggering processes that generate other harmful molecules. For example, they can prompt the production of free radicals, which are also highly reactive and can cause DNA damage similarly.

Like a good mechanic fixing problems in a car's engine, vigorous and sustained exercise helps our body repair some of these damages effectively, reversing the signs of aging. It achieves this by reducing levels of different ROS that accumulate with age. One such ROS targeted is 8-hydroxy-2'-deoxyguanosine (8-OHdG). When 8-OHdG builds up, it alters the DNA sequence, affecting its capacity to code for functional proteins. In bacteria, a special protein known as formamidopyrimidine-DNA glycosylase (Fpg) functions like an 'eraser' and removes 8-OHdG tags from the DNA.

A homologous protein known as OGG1 mediates the same function in mammals, including humans. Vigorous exercise training activates OGG1 and hence helps remove 8-OHdG from the DNA. This relationship between exercise, OGG1 activity, and 8-OHdG levels was unraveled in a study involving middle-aged (20-month-old) and old-aged (30-month-old) rats. Both groups of rats engaged in eight weeks of treadmill running. Levels of both OGG1 and 8-OHdG were measured. Overall, they found a simultaneous increase in OGG1 and a decrease in 8-OHdG with increased duration of exercise in the gastrocnemius, one of the rats' major muscles in the calf of the leg [34].

Overall, vigorous exercise contributes to longevity by reducing the incidence of chronic diseases and mediating anti-aging effects. It achieves this by lowering levels of ROS like 8-OHdG that otherwise compromise the integrity of the DNA sequence.

Finding Your Fitness Formula: Balancing Vigorous Exercise with Zone 2 Training for Optimal Health

The burning question remains…How do I find the right balance between vigorous exercise and moderate-intensity Zone 2 training? The answer depends on individual goals, preferences, and consistency. Establishing a habit of regular exercise is crucial, irrespective of the specific type.

For instance, endurance athletes typically follow the '80/20 rule', dedicating about 20% of their training to shorter, higher intensity workouts and the latter to Zone 2 training. However, this may not apply universally, especially for those exercising less than 10 hours a week.

Fortunately, several training protocols are available to improve VO2 max and acquire fitness benefits. As suggested in Dr. Rhonda Patrick’s podcast, a particularly effective protocol is the 'Norwegian 4X4 interval training.' The training involves a warmup, followed by four 4-minute intervals (again, where your heart rate reaches past 80 percent of its maximum capacity), each interspersed with a three-minute recovery period and finished off with a cool-down. [2]

Apart from the Norwegian protocol, another protocol discussed that has gained much traction is the 'one minute on/one minute off' protocol. It involves alternating between one minute of intense exercise and one minute of rest or active recovery. During the one-minute interval, you should aim to work at a high intensity, such as sprinting, cycling at high resistance, or performing burpees or jumping jacks. During the one-minute off interval, you can rest entirely or engage in low-intensity activity, such as walking or jogging slowly.

The choice of protocol depends on your comfort levels and time commitment. The latter protocol has gained more traction amongst the lay public as it is less grueling regarding the duration of high-intensity interval training. Irrespective of the choice of training selected, the fundamental goal is to have an exercise routine involving long intervals, at least 1 minute, at the highest sustainable intensity.


Overall, vigorous exercise, characterized by activities that significantly elevate heart rate and energy expenditure, emerges as a formidable deterrent against aging, heart disease, and cancer. Dedicating as little as 15 minutes per week to vigorous exercise has been associated with an 18% decrease in mortality risk, showcasing its remarkable impact on overall longevity.

The association between vigorous physical exercise and decreased heart disease is particularly noteworthy. Vigorous exercise consistently helps manage risk factors associated with CHD, such as high blood pressure, triglyceride levels, HDLs, obesity, CRP, and smoking. Through mechanisms like reducing blood pressure, elevating HDL levels, and diminishing inflammation, vigorous exercise emerges as a proactive strategy for maintaining cardiovascular health.

Apart from the heart, it also works against cancer. Moderate exercise for 3 to 5 hours per week significantly lowers the risk of various cancers, including breast, colorectal, esophageal, kidney, stomach, and endometrial. It accomplishes these anti-cancer effects by curbing insulin, reducing inflammation, boosting the immune system, modifying bile production, and improving digestion.

Finally, vigorous exercise also exerts anti-aging effects by attenuating ROS-precipitated DNA damage.

As society grapples with the challenges of an aging population, embracing vigorous exercise stands out as a proactive and accessible means to champion health and longevity.


  • High-intensity vigorous exercise includes physically demanding activities that elevate heart rate and energy expenditure. This type of exercise causes the heart to beat at 70% to 85% of your maximum heart rate. Examples include running, swimming laps, aerobic dancing, and cycling at a fast pace.

  • High-Intensity Interval Training (HIIT) is a form of vigorous exercise involving alternating periods of high-intensity exercise and intervals of lower-intensity exercise or rest.

  • HIIT engages both aerobic and anaerobic energy systems, making it a comprehensive workout that boosts overall fitness.

  • It is known for enhancing VO2 Max, which is the maximum amount of oxygen the body can utilize during intense exercise.

  • Vigorous Exercise and Brain Health: Vigorous exercise promotes the production of lactate, which is a beneficial fuel for the brain.

  • Increased lactate production supports neuron energy, aids in neurotransmitter release, and conserves glucose for other essential brain functions.

  • Vigorous Exercise and Heart Health: Regular vigorous exercise can lower the risk of heart disease, manage risk factors associated with coronary heart disease (CHD), and reduce conditions like high blood pressure and obesity.

  • Vigorous Exercise may also reverse heart aging, making the hearts of older individuals more efficient and resilient.

  • Vigorous Exercise and Cancer: Vigorous exercise is linked to a reduced risk of various cancers including breast, colorectal, and endometrial cancer. It works by improving blood flow, lowering levels of certain hormones, curbing elevated insulin levels, reducing inflammation, and boosting the immune system.

  • Vigorous Exercise and Aging: Vigorous exercise has anti-aging effects, aiding in the repair of DNA damage caused by reactive oxygen species (ROS). It lowers levels of harmful ROS and promotes the activation of proteins like OGG1, which helps remove damaging tags from DNA, thus preserving its integrity.


  1. Yang Y. J. (2019). An Overview of Current Physical Activity Recommendations in Primary Care. Korean journal of family medicine, 40(3), 135–142.

  2. YouTube. (2023). YouTube. Retrieved December 18, 2023, from

  3. Harvard T.H. Chan School of Public Health. (2019, January 11). Staying Active. The Nutrition Source.

  4. Patel, H., Alkhawam, H., Madanieh, R., Shah, N., Kosmas, C. E., & Vittorio, T. J. (2017). Aerobic vs. aerobic exercise training effects on the cardiovascular system. World journal of cardiology, 9(2), 134–138.

  5.  Scribbans, T. D., Vecsey, S., Hankinson, P. B., Foster, W. S., & Gurd, B. J. (2016). The Effect of Training Intensity on VO2max in Young Healthy Adults: A Meta-Regression and Meta-Analysis. International journal of exercise science, 9(2), 230–247.

  6. Kokkinos P, Myers J, Faselis C, Panagiotakos DB, Doumas M, Pittaras A, Manolis A, Kokkinos JP, Karasik P, Greenberg M, Papademetriou V, Fletcher R. Exercise capacity and mortality in older men: a 20-year follow-up study. Circulation. 2010 Aug 24;122(8):790-7. doi: 10.1161/CIRCULATIONAHA.110.938852. Epub 2010 Aug 9. PMID: 20697029.

  7. Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013 Jul;93(3):993-1017. doi: 10.1152/physrev.00038.2012. PMID: 23899560.

  8. Boutcher SH. High-intensity intermittent exercise and fat loss. J Obes. 2011;2011:868305. doi: 10.1155/2011/868305. Epub 2010 Nov 24. PMID: 21113312; PMCID: PMC2991639.

  9. LaForgia J, Withers RT, Gore CJ. Effects of exercise intensity and duration on the excess post-exercise oxygen consumption. J Sports Sci. 2006 Dec;24(12):1247-64. doi: 10.1080/02640410600552064. PMID: 17101527.

  10. Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5618-23. doi: 10.1073/pnas.0501559102. Epub 2005 Mar 30. PMID: 15800038; PMCID: PMC556267.

  11. Hood, D. A., Uguccioni, G., Vainshtein, A., & D'souza, D. (2011). Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle: implications for health and disease. Comprehensive Physiology.

  12. Tunstall RJ, Mehan KA, Wadley GD, Collier GR, Bonen A, Hargreaves M, Cameron-Smith D. Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol Endocrinol Metab. 2002 Jul;283(1):E66-72. doi: 10.1152/ajpendo.00475.2001. PMID: 12067844.

  13. Palikaras K, Lionaki E, Tavernarakis N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat Cell Biol. 2018 Sep;20(9):1013-1022. doi: 10.1038/s41556-018-0176-2. Epub 2018 Aug 28. PMID: 30154567.

  14. Brooks GA. Cell-cell and intracellular lactate shuttles. J Physiol. 2009 Dec 1;587(Pt 23):5591-600. doi: 10.1113/jphysiol.2009.178350. Epub 2009 Oct 5. PMID: 19805739; PMCID: PMC2805372.

  15. Liu PZ, Nusslock R. Exercise-Mediated Neurogenesis in the Hippocampus via BDNF. Front Neurosci. 2018 Feb 7;12:52. doi: 10.3389/fnins.2018.00052. PMID: 29467613; PMCID: PMC5808288.

  16. Wu A, Lee D, Xiong WC. Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases. Int J Mol Sci. 2023 Aug 29;24(17):13398. doi: 10.3390/ijms241713398. PMID: 37686202; PMCID: PMC10487923.

  17. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002 Nov 7;347(19):1483-92. doi: 10.1056/NEJMoa020194. PMID: 12421890.

  18. Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, Suzuki E, Shimano H, Yamamoto S, Kondo K, Ohashi Y, Yamada N, Sone H. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. Arch Intern Med. 2007 May 28;167(10):999-1008. doi: 10.1001/archinte.167.10.999. PMID: 17533202.

  19. Lakka TA, Lakka HM, Rankinen T, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study. Eur Heart J. 2005 Oct;26(19):2018-25. doi: 10.1093/eurheartj/ehi394. Epub 2005 Jun 29. PMID: 15987707.

  20. Howden EJ, Sarma S, Lawley JS, Opondo M, Cornwell W, Stoller D, Urey MA, Adams-Huet B, Levine BD. Reversing the Cardiac Effects of Sedentary Aging in Middle Age-A Randomized Controlled Trial: Implications For Heart Failure Prevention. Circulation. 2018 Apr 10;137(15):1549-1560. doi: 10.1161/CIRCULATIONAHA.117.030617. Epub 2018 Jan 8. PMID: 29311053; PMCID: PMC5893372.

  21. Boström, P., Wu, J., Jedrychowski, M. et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012).

  22. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008 Dec;8(12):915-28. doi: 10.1038/nrc2536. Erratum in: Nat Rev Cancer. 2009 Mar;9(3):224. PMID: 19029956.

  23. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004 Apr 24;363(9418):1346-53. doi: 10.1016/S0140-6736(04)16044-3. PMID: 15110491.

  24. Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc. 2001 Feb;60(1):91-106. doi: 10.1079/pns200070. PMID: 11310428.

  25. Coussens, L., Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).

  26. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008 Oct;88(4):1379-406. doi: 10.1152/physrev.90100.2007. PMID: 18923185.

  27. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010 Mar 19;140(6):883-99. doi: 10.1016/j.cell.2010.01.025. PMID: 20303878; PMCID: PMC2866629.

  28. Friedenreich CM, Neilson HK, Lynch BM. State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer. 2010 Sep;46(14):2593-604. doi: 10.1016/j.ejca.2010.07.028. PMID: 20843488.

  29. Nieman DC, Wentz LM. The compelling link between physical activity and the body's defense system. J Sport Health Sci. 2019 May;8(3):201-217. doi: 10.1016/j.jshs.2018.09.009. Epub 2018 Nov 16. PMID: 31193280; PMCID: PMC6523821.

  30. Pedersen L, Idorn M, Olofsson GH, Lauenborg B, Nookaew I, Hansen RH, Johannesen HH, Becker JC, Pedersen KS, Dethlefsen C, Nielsen J, Gehl J, Pedersen BK, Thor Straten P, Hojman P. Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metab. 2016 Mar 8;23(3):554-62. doi: 10.1016/j.cmet.2016.01.011. Epub 2016 Feb 16. PMID: 26895752.

  31. Campbell JP, Turner JE. Debunking the Myth of Exercise-Induced Immune Suppression: Redefining the Impact of Exercise on Immunological Health Across the Lifespan. Front Immunol. 2018 Apr 16;9:648. doi: 10.3389/fimmu.2018.00648. PMID: 29713319; PMCID: PMC5911985.

  32. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011 Aug 5;11(9):607-15. doi: 10.1038/nri3041. PMID: 21818123.

  33. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014 May;58(2-3):193-210. doi: 10.1007/s12026-014-8517-0. PMID: 24798553

  34. Nakamoto, H., Kaneko, T., Tahara, S., Hayashi, E., Naito, H., Radak, Z., & Goto, S. (2007). Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and modulates the DNA repair activity in the liver of old rats. Experimental gerontology, 42(4), 287–295.


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