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How human connection helps break the addiction cycle.

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In an increasingly widely disseminated TED Talk titled " Everything You Think You Know About Addiction is Wrong," British journalist Johann Hari discusses the available research into the underlying causes of addiction and concludes, rather brilliantly, that the opposite of addiction is not sobriety, it's connection. His statement echoes a theme that I and many 21st Century addiction specialists have espoused for years - that addiction is not about the pleasurable effects of substances, it's about the user's inability to connect in healthy ways with other human beings. In other words, addiction is not a substance disorder, it's a social disorder.

This, of course, is contrary to what most folks believe about substance abuse. In general, people think that the pleasurable effects of alcohol, cocaine, heroin, and the like are the primary drivers of addiction. And why not? We know for certain that once ingested these substances trigger the release of dopamine and several other pleasure-related neurochemicals into the brain. In other words, potentially addictive substances make us feel good, and because we like to feel good, we tend to go back for more.

Hence, the human propensity for addiction. Or so it seems at first glance. Bolstering this belief is the fact that most of the early research and theories on the root causes of addiction are centered on the brain's pleasure response - the aforementioned dopamine rush. Even the National Institute on Drug Abuse initially espoused this view.[i]

Nevertheless, this long-held belief is incorrect. If it wasn't, then everybody who ever took a sip of alcohol would become a raging drunk, and everyone who ever ingested an opiate (even via prescription) would end up in a back alley shooting heroin. But that isn't even close to what actually happens. In reality, only about 10 percent of the people who try a potentially addictive substance eventually become addicted. The rest of the people either walk away from the substance completely or continue to enjoy it casually or recreationally.
Welcome to the Rat Park
Given the above, one wonders what is really going on with addiction. Obviously, there is more to the equation than just the dopamine pleasure response. Certainly, the experience of pleasure does play some role, because it opens the doorway to addiction. But it is clear, based on the fact that most people do not become addicts, that over time a person's initial experience of pleasure is not what causes that individual to return to an addictive substance again and again, compulsively and to his or her detriment.

This is a conundrum that scientists began to explore in the late-1970s and early-1980s. For instance, Canadian psychologist Bruce Alexander looked at the results of studies in which rats were placed in empty cages, alone, with two water bottles to choose from - one with pure water, the other with heroin-infused water. Those experiments showed that as time passed these rats would uniformly get hooked on and eventually overdose from heroin. So the researchers unsurprisingly concluded that the potential of extreme pleasure, in and of itself, is addictive. Case closed, right?

Not for Alexander. He was bothered by the fact that the cages in which the rats were isolated were small, with no potential for stimulation beyond the heroin. Alexander thought: Of course they all got high. What else were they supposed to do? In response to this perceived shortcoming, Alexander created what we now call "the rat park," a cage approximately 200 times larger than the typical isolation cage, with Hamster wheels and multi-colored balls to play with, plenty of tasty food to eat, and spaces for mating and raising litters.[ii] And he put not one rat, but 20 rats (of both genders) into the cage.

Then, and only then, did he mirror the old experiments, offering one bottle of pure water and one bottle of heroin water. And guess what? The rats ignored the heroin. They were much more interested in typical communal rat activities such as playing, fighting, eating, and mating. Essentially, with a little bit of social stimulation and connection, addiction disappeared. Heck, even rats who'd previously been isolated and sucking on the heroin water left it alone once they were introduced to the rat park.
The Human Rat Park
One of the reasons that rats are routinely used in psychological experiments is that they are social creatures in many of the same ways that humans are social creatures. They need stimulation, company, play, drama, sex, and interaction to stay happy. Humans, however, add an extra layer to this equation. We need to be able to trust and to emotionally attach.

This human need for trust and attachment was initially studied and developed as a psychological construct in the 1950s when John Bowlby tracked the reactions of small children when they were separated from their parents.[iii] In a nutshell, he found that infants, toddlers, and young children have an extensive need for safe and reliable caregivers. If children have that, they tend to be happy in childhood and well-adjusted (emotionally healthy) later in life. If children don't have that, it's a very different story.

It is clear from Bowlby's work and the work of later researchers that the level and caliber of trust and connection experienced in early childhood carries forth into adulthood. Those who experience secure attachment as infants, toddlers, and small children nearly always carry that with them into adulthood, and they are naturally able to trust and connect in healthy ways. Meanwhile, those who don't experience secure early-life attachment tend to struggle with trust and connection later in life. In other words, securely attached individuals tend to feel comfortable in and to enjoy the human rat park, while insecurely attached people typically struggle to fit in and connect.
Guess which group is more vulnerable to addiction?
The good news is that people with insecure attachment styles are not locked into this approach for life. With proper guidance and a fair amount of conscious effort the individuals who were not graced with secure attachment in childhood (and therefore the ability to easily connect in adulthood) can learn to securely attach - usually through therapy, support groups, and various other healthy and healing relationships - creating over time what is known as "earned security."

For the addicted, earned security is a very important concept. Rats don't really need it. You can take an addicted rat and toss him into the rat park and he will quickly and easily assimilate, pushing his addiction to the curb in favor of healthier rat connections and activities. But people? Not so much. With the addicted, there is further work to be done, and part of that work nearly always involves overcoming the lack of trust and connection created in childhood.

Interestingly, both AA and the addiction treatment community as a whole realized this fact long before Alexander's rat park experiment. In truth, the often parallel work of 12-step recovery programs and formalized addiction treatment programs - after the initial experience of detox - involves connecting the addict to other people. And not just any people, either. We're talking about safe, supportive, reliable, empathetic people.

Much of the time these safe and supportive people are other addicts in recovery who know exactly what it feels like to be addicted and to embark on the lengthy process of healing. However, this newfound sense of connection doesn't always have to be with other recovering addicts. For instance, as Hari discusses in his TED Talk, the nation of Portugal, which decriminalized illicit substances (i.e., addictive drugs) in 2001, takes a broader-than-normal approach to overcoming addiction. Instead of spending money on incarceration, Portugal has focused its efforts on helping addicts connect with society at large.

If, for instance, the addicted was a computer programmer prior to his or her downfall, the government will find a company that needs a computer programmer and offer to pay half of the addict's salary for the first year of employment if the company will give that person a shot. Additionally, the government funds traditional treatment opportunities and various other forms of social support. In short, Portugal tries to reintegrate addicts into the human rat park in a way that helps them learn to trust and connect.

And it's working, too. Contrary to most doomsayer predictions, decriminalization in Portugal did not lead to an increase in drug use, addiction, and related problems. In fact, the opposite occurred. Problematic drug use is down, drug use among adolescents is down, drug-related deaths and other drug-related harms are down, jail/prison overcrowding is down, etc.[iv] That said, things are not perfect. For instance, there are reports that cannabis use is up, and that more people are reporting lifetime usage of it.[v] (This may be a matter of people equating marijuana with alcohol, and, now that it's legal, simply preferring to smoke rather than drink.) But overall it looks like Portugal's unprecedented strategy of connecting rather than isolating problem drug users has been effective.

So it does indeed appear that the opposite of addiction is not sobriety, it's connection. That said, developing healthy interpersonal connections as a part of recovery and healing is not easy. It takes time, effort, and a willing support network. The good news is that we now know for certain that this type of recovery and social connection is possible - even for the most problematic of addicts.

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In an increasingly widely disseminated TED Talk titled " Everything You Think You Know About Addiction is Wrong," British journalist Johann Hari discusses the available research into the underlying causes of addiction and concludes, rather brilliantly, that the opposite of addiction is not sobriety, it's connection.

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Why we make bad decisions even when we know we shouldn't -- and discusses a couple tricks that could get us to do the right thing (even if it's for the wrong reason). Relating to the Transtheoretical model of change.

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Dan Ariely: How to change your behavior for the better

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What's the best way to get people to change their behavior? In this funny, information-packed talk, psychologist Dan Ariely explores why we make bad decisions even when we know we shouldn't -- and discusses a couple tricks that could get us to do the right thing (even if it's for the wrong reason).

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Diet, relaxation techniques, physical activity, inner voice, human connection, laughing, and sleep all have effects on our stress and the prevention of it becoming chronic.

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Stress is part of being human, and it can help motivate you to get things done. Even high stress from serious illness, job loss, a death in the family, or a painful life event can be a natural part of life. You may feel down or anxious, and that's normal too for a while.

Talk to your doctor if you feel down or anxious for more than several weeks or if it starts to interfere with your home or work life. Therapy, medication, and other strategies can help.

In the meantime, there are things you can learn to help you manage stress before it gets to be too much. These tips may help you keep stress at bay:

Keep a positive attitude.

Accept that there are events that you cannot control.

Be assertive instead of aggressive. Assert your feelings, opinions, or beliefs instead of becoming angry, defensive, or passive.

Learn to manage your time more effectively.

Set limits appropriately and say no to requests that would create excessive stress in your life.

Make time for hobbies and interests.

Don't rely on alcohol, drugs, or compulsive behaviors to reduce stress. Drugs and alcohol can stress your body even more.

Seek out social support. Spend enough time with those you love.

Seek treatment with a psychologist or other mental health professional trained in stress management or biofeedback techniques to learn more healthy ways of dealing with the stress in your life.

There's a lot more you can do to help manage stress. Consider these lifestyle changes:

To start with, physical activity can help improve your sleep. And better sleep means better stress management. Doctors don't yet know exactly why, but people who exercise more tend to get better deep "slow wave" sleep that helps renew the brain and body. Just take care not to exercise too close to bedtime, which disrupts sleep for some people.

Exercise also seems to help mood. Part of the reason may be that it stimulates your body to release a number of hormones like endorphins and endocannabinoids that help block pain, improve sleep, and sedate you. Some of them (endocannabinoids) may be responsible for the euphoric feeling, or "runner's high," that some people report after long runs.

People who exercise also tend to feel less anxious and more positive about themselves. When your body feels good, your mind often follows. Get a dose of stress relief with these exercises:

If you don't have the time for a formal exercise program, you can still find ways to move throughout your day. Try these tips:

Bike instead of driving to the store.

Use the stairs instead of the elevator.

Park as far as you can from the door.

Hand-wash your car.

Clean your house.

Walk on your lunch break.

The benefits of eating health foods extend beyond your waistline to your mental health. A healthy diet can lessen the effects of stress, build up your immune system, level your mood, and lower your blood pressure. Lots of added sugar and fat can have the opposite effect. And junk food can seem even more appealing when you're under a lot of stress.

To stay healthy and on an even keel, look for complex carbohydrates, lean proteins, and fatty acids found in fish, meat, eggs, and nuts.

Antioxidants help too. They protect your cells against damage that chronic stress can cause. You can find them in a huge variety of foods like beans, fruits, berries, vegetables, and spices such as ginger.

Stick to a healthy diet with a few simple tips. Make a shopping list. Carry healthy snacks with you when you leave the house. Stay away from processed foods, and try not to eat mindlessly.

Scientists have pinpointed some nutrients that seem to help lessen the effects of stress on the body and mind. Be sure to get enough these as part of a balanced diet:

A common side effect of stress is that you may struggle to fall asleep. If this happens three times a week for at least 3 months, you may have insomnia, an inability to fall and stay asleep. Lack of sleep can also add to your stress level and cause a cycle of stress and sleeplessness.

Better sleep habits can help. This includes both your daily routine and the way you set up your bedroom. Habits that may help include:

Exercise regularly.

Get out in the sunlight.

Drink less alcohol and caffeine close to bedtime.

Set a sleep schedule.

Don't look at your electronics 30-60 minutes before bed.

Try meditation or other forms of relaxation at bedtime.

The role of your bedroom in good sleep hygiene also is important. In general, your room should be dark, quiet, and cool. Your bed also plays an important role. Your mattress should provide support, space and most of all, comfort.

Yoga. This is a form of exercise, but it can also be a meditation. There are many types of yoga. The ones that focus on slow movement, stretching, and deep breathing are best for lowering your anxiety and stress.

Meditation. It has been around for over 5,000 years for a reason. Meditation works well for many people and has many benefits. It can lower stress, anxiety, and chronic pain as well as improve sleep, energy levels, and mood. To meditate, you will need to:

1. Find a quiet place.

2. Get comfortable (sitting or lying down).

3. Focus your attention on a word, phrase, object, or even your breath.

4. Let your thoughts come and go and do not judge them.

Deep breathing. When you practice deep breathing, you turn on your body's natural ability to relax. This creates a state of deep rest that can change how your body responds to stress. It sends more oxygen to your brain and calms the part of your nervous system that handles your ability to relax.

Try belly breathing. Get comfortable, close your eyes, and place one hand on your stomach and the other on your chest. Take a deep breath in through your nose. You should feel your belly rise more than your chest. Now, exhale through your nose and pay close attention to how your body relaxes. Repeat.

Biofeedback. Learn how to manage your heart rate, muscle tension, and blood pressure when stress hits. Biofeedback gives you information about how your body reacts when you try to relax. Sensors are placed on your body that call out changes in everything from your brain-wave pattern to your muscle tone. Working with a biofeedback therapist, you can start to take control of the signals by changing how your body reacts to the sensor.

Connect with people. Spend time with a friend or family member who will listen to you. It is a natural way to calm you and lower your stress. When you connect with people in person, your body releases a hormone that stops your fight-or-flight response. You relax.

Behavior. How you respond to people directly impacts your stress levels. Manage your response with these tips:

Try not to overcommit yourself

Share the responsibility

Count to 10 before you respond

Walk away from a heated situation

Distract yourself with music or podcasts

Inner voice. Nothing affects your stress levels like the voice inside your head. The good news is you are in control. You can exchange negative thoughts for positive ones. There are more benefits to positive self-talk than reducing stress. These include a longer life, lower levels of depression, greater resistance to the common cold and cardiovascular disease, and better coping skills for when hard times hit.

Laugh therapy. When you laugh, you take in more oxygen. Your heart, lungs, and muscles get a boost and your body releases those feel-good hormones. Laughter also improves your immune system, lessens pain, and improves your mood for long periods of time.

Talk therapy. Long-term talk therapy helps some people deal with stress. One approach, cognitive behavioral therapy, helps you change negative thought patterns. Your therapist can guide you toward other approaches that might be helpful.

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Before stress takes a toll on your health, learn how you can keep it under control and manage it.

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Goes over the five components of physical fitness (1) body composition, (2) flexibility, (3) muscular strength, (4) muscular endurance, and (5) cardiorespiratory endurance.

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Study explains the physiological effects that lack of exercise has on stress and how being sedentary aids in chronic stress developing.

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Abstract

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO ₂ max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.

1. Organization of article

1.1 Entire article

An underappreciated primary cause of most chronic conditions is the lack of sufficient daily physical activity ("physical inactivity"). Overwhelming evidence proves the notion that reductions in daily physical activity are primary causes of chronic diseases/conditions and that physical activity/exercise is rehabilitative treatment (therapy) from the inactivity-caused dysfunctions. The general strategy of presentation divides the article into three major sections: 1) Conceptual information forming the foundation to understand the remaining article; 2) Primary literature supporting physical inactivity as a primary cause to a myriad of chronic conditions/diseases, and 3) additional considerations. The aim of the entire article is to bring better understanding and insight into the observation that a lack of physical activity at ancestral levels initiates 35 pathological and clinical conditions.

1.2 First third of article

Conceptual information is presented in five parts in the first third of the article. 1) Definitions of forms of physical activity, functional capacity, types of fitness, chronic diseases, types of prevention so that the reader understands how the article employs these words; 2) A brief chronology of the three-millennia history that recognizes that physical inactivity reduces functional capacity and health; 3) Cause vs. treatment are discussed to emphasize that physical inactivity is a primary cause of chronic conditions/diseases; 4) Growing evidence that mechanisms by which inactivity causes disease differ from mechanisms by which physical activity is a therapy/treatment to act as a primary preventer of disease; and 5) Gene-environment interactions have varying degrees of gene involvement in the magnitude of change to physical activity.

1.3 Center portion of article

Physical inactivity is a primary cause initiating 35 separate pathological and clinical conditions. Many of the 35 conditions are subdivided under major categories, such as loss of functional capacities with chronological aging; metabolic syndrome, obesity, insulin resistance, prediabetes/type 2 diabetes, non-alcoholic liver disease, cardiovascular diseases, cognitive functions and diseases, bone and connective tissue disorders, cancer, reproductive diseases, and diseases of digestive tract, pulmonary, and kidney.

1.4 Final portion of article

The article ends with considerations of clinical significance, increasing risk factors during long-term sedentarism, the developmental and clinical consequences of inactive childhood/adolescence, and policy.

2. Definitions

2.1 CDC definitions of forms of physical activity

Verbatim definitions for exercise and health are from the US Centers for Disease Control and Prevention (CDC) are used where possible due to the authority they carry ( 90). US governmental definitions were selected for the article to provide the framework for this article's discussions of how 1) exercise/physical activity prevents chronic diseases and 2) lack of physical activity is a primary event that causes chronic diseases.

Health-enhancing physical activity

"Activity that, when added to baseline activity, produces health benefits. Brisk walking, jumping rope, dancing, playing tennis or soccer, lifting weights, climbing on playground equipment at recess, and doing yoga are all examples of health-enhancing physical activity", as defined by CDC ( 90).

As previously stated, this article will concentrate on the use of physical activity to prevent physical inactivity, and, thus, prevent many chronic diseases.

2.2 Definition of physical inactivity

CDC definitions for exercise do not include a definition of "physical inactivity". We define physical inactivity as "physical activity levels less than those required for optimal health and prevention of premature death". Further consideration of the definition is given in section entitled, "Prevention of death by primary prevention of physical inactivity".

2.3 Definition of functional capacity

We define "functional capacity" as the ability of a cell, organ, system, or body to maintain homeostasis within their narrow limits of survival in response to a specified stress. If an external stress disrupts homeostasis beyond an organism's functional capacity, life may not be sustained. Diminished ability to adapt to stressors increases the likelihood of death. Functional capacity is pliable; declining rapidly with extreme physical inactivity or more slowly with aging, while preventing inactivity can increase functional capacity (considered in specific detail in the aging section). Importantly, a direct relationship between functional capacity and survival is a cornerstone of general medicine theory. A major predictor of functional capacity is maximal aerobic capacity (VO ₂max), which while directly testing cardiovascular fitness and integrity also represents a combination of other physiologic components. For instance, VO ₂max also depends on pulmonary and muscle function, health status of other organ systems, nutritional status, medications, orthopedic limitations, and others ( 352). An aerobic functional capacity in patients under 4-metabolic equivalents (METs), a typical demand during normal daily activities, increases postoperative (time from admission to discharge from surgery) cardiac and long-term risks ( 155). In another study, patients were grouped by MET capacity in relationship to complication prevalence after they underwent angiographically verified coronary artery disease and subsequent open abdominal nonvascular surgery. ( 265). Those from the group < 4 METs had cardiologic complications in 64% of cases, the 4-7 METs group had 29%, and the 7-10 METs group had 8%. These remarkable findings can be extrapolated to other stresses where the probability of complications, and even survival, is dependent upon the functional capacity needed to maintain homeostasis.

2.4 Physical fitness vs. physical activity

Some people incorrectly use physical fitness and physical activity interchangeably. The CDC defines physical fitness as "The ability to carry out daily tasks with vigor and alertness, without undue fatigue, and with ample energy to enjoy leisure-time pursuits and respond to emergencies. Physical fitness includes a number of components consisting of cardiorespiratory endurance (aerobic power), skeletal muscle endurance, skeletal muscle strength, skeletal muscle power, flexibility, balance, speed of movement, reaction time, and body composition". The CDC defines physical activity as "Any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level" ( 90)..

Inherited genes and their interaction with physical activity levels determine physical fitness. However, chronic physical activity levels themselves modulate fitness. Further, the levels of physical activity, themselves, modulate whether fitness improves. For example, Sisson et al. ( 478) concluded that the most important finding of their study was that greater volumes of exercise were associated with a lower probability of being a nonresponder. The percentage of non-responders at a given level of training progressively decreased as the exercise volume increased.

2.5 Cardiorespiratory fitness (CRF)

We define CRF as the capacity of the cardiovascular (heart and blood vessels) and respiratory (lungs) systems to supply oxygen-rich blood to the working skeletal muscles and the capacity of the muscles to use oxygen to produce energy for movement. The gold standard to determine CRF is the aforementioned VO ₂max, or maximum aerobic fitness. However in large clinical human studies, an acceptable surrogate for VO ₂max is the length of time running or cycling in standardized test, assuming appropriate physiological/biochemical/psychological proof of exhaustion is obtained ( 65, 263).

The majority of data about fitness and physical activity is focused on aerobic fitness. Data indicates that rapid, severe physical inactivity can rapidly decrease CRF. For instance, in the Dallas Bed Rest study, healthy, young males' VO ₂max decreased 27% after 20 days of continuous bed rest ( 454) and another study in Denmark 2 weeks of reducing daily step number from 10,501 to 1344 VO ₂max decreased 7% ( 389).

2.7 Balance and flexibility fitness

We define balance fitness as the ability to control the body's position throughout movement,and flexibility fitness as the ability to achieve an extended range of motion. Both have components of genetic inheritability and are also trainable (Discussed later in Twin studies-Modulation of twin health by physical activity).

2.8 Definition of chronic diseases and their prevalence

We define chronic disease as a disease slow in its progress (decades) and long in its continuance, as opposed to acute disease, which is characterized by a swift onset and short course.

Medicine, public health, pharmaceutical industry, and educational systems have reduced infectious diseases and early life mortality resulting in record average life spans for much of the human population. In place of infectious diseases most people in the US now die of chronic diseases.

The CDC Website states, "Chronic diseases-such as heart disease, cancer, and diabetes-are the leading causes of death and disability in the United States. Chronic diseases account for 70% of all deaths in the U.S., which is 1.7 million each year ( 85). These diseases also cause major limitations in daily living for almost 1 out of 10 Americans or about 25 million people ( 85), The CDC further wrote, "Chronic diseases - such as heart disease, stroke, cancer, diabetes, and arthritis - are among the most common, costly, and preventable of all health problems in the U.S." ( 86). In addition to the CDC, former US Secretary of Health and Human Services, the Honorable Michael O. Leavitt in the 2008 Physical Activity Guidelines for Americans, wrote,

Along with President Bush, I believe that physical activity should be an essential component of any comprehensive disease prevention and health promotion strategy for Americans. We know that sedentary behavior contributes to a host of chronic diseases, and regular physical activity is an important component of an overall healthy lifestyle. There is strong evidence that physically active people have better health-related physical fitness and are at lower risk of developing many disabling medical conditions than inactive people ( 532).

2.9 Definitions of types of prevention

For the purposes of this article, physical activity is presented as primary prevention of physical inactivity. The CDC defines physical inactivity as an actual cause of chronic conditions ( 213, 345). Physical activity, itself, rarely causes chronic conditions, e.g., participation in specific sports improves general health, but can increase the risk of osteoarthritis in specific populations ( 71); discussed later in section "Osteoarthritis". The next definitions are taken from a commissioned paper by the U.S. Institute of Medicine ( 267).

2.11 Application of exercise to prevention categories

Examples for our view that exercise is a primary, secondary, and tertiary preventer of disease are as follows: 1) Primary prevention (direct treatment of cause to prevent disease occurrence) is voluntary avoidance of physical inactivity or treatment of physical inactivity with physical activity; 2) Secondary treatment [eliminating one cause (physical inactivity) of existing hypertension by eliminating physical inactivity] is treatment of existing hypertension with physical activity; and 3) Tertiary prevention with physical activity is cardiac rehabilitation where exercise benefits do not reverse the anatomical pathology from myocardial infarction. We propose that the greatest health benefit of physical activity is primary prevention of 35 chronic diseases/conditions to become clinically overt. This article is largely restricted to consideration of primary prevention of inactivity as an actual cause of chronic conditions.

3. Overview for next three sections

While, concerns that physical inactivity is detrimental to health have been documented for over three millennia, much remains unknown, e.g., a) how to change the sedentary behavior of the 92% of U.S. adolescents and > 95% of adults who do not met the U.S. Department of Health and Human Services guidelines for physical activity ( 527), b) how to have health care professionals provide effective individualized exercise prescriptions, and c) what are the molecular links between inactivity and chronic disease that will provide a policy tool in the same way as the molecular link between the carcinogen in tobacco and lung cancer did ( 129).

4. Summary of daily step reductions from antiquity

Historical evidence shows that physical inactivity is prevalent in today's society relative to historical levels ( 385). Estimated daily step numbers have declined ~50% to ~70% since the introduction of powered machinery. ( Table 1 ).

Table 1

Population

Year

Steps per day

References

5. History of inactivity's compromising effects on function and health

Three millennia of evidence exist to indicate historical recognition that physical inactivity is detrimental to health by reducing the functional capacity of most organ systems in humans, mammals, and rodents.

5.2 Hippocrates (~450 BC)

Quotations attributed to Hippocrates promote the primary prevention of disease by physical activity.

"If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health" ( 240).

"If there is any deficiency in food and exercise the body will fall sick" ( 477).

"Walking is man's best medicine" ( 240).

"All parts of the body, if used in moderation and exercised in labors to which each is accustomed, become thereby healthy and well developed and age slowly; but if they are unused and left idle, they become liable to disease, defective in growth and age quickly" ( 278).

5.4 Initial epidemiology (1949-1953)

Jeremiah Morris is recognized as the person who first used physical activity in epidemiology (his history is available ( 43). In 1953, Morris and co-workers compared bus drivers, who are sedentary in their occupation, with the physically active bus conductors, who were constantly moving up and down double-decker buses to collect fares in London. Physically active conductors had a 30% lower incidence rate of coronary heart disease (CHD) than the physically inactive bus drivers ( 353). Furthermore, even the physically active conductors who did develop CHD with age were better off, presenting with less severe disease and lower fatality rates than the inactive bus drivers ( 353). However, while VO ₂max was not determined in Morris' report, others have since shown that workers in physically active occupations have higher aerobic capacity than their inactive peers ( 220). Morris' 1953 report ( 353) is a milestone as the initial publication documenting daily physical inactivity is associated with increased morbidity and mortality ( 43).

In his 10 th decade of Morris' life, he wrote, "We in the West are the first generation in human history in which the mass of the population has to deliberately exercise to be healthy. How can society's collective adaptations match?" ( 43, 354).

5.5 Primary prevention: Human space flight (1957-1961)

The Space Race for national security began in earnest in 1954 leading to the successful launch and orbit of Sputnik from the USSR on October 4, 1957. Four years later on April 12, 1961 Yuri Gagarin became the first human in outer space and the first to orbit the Earth. The Space Race hastened physiological exploration that the microgravity experienced in space reduced human functional capacities. As an outcome, NASA researched countermeasures to the microgravity-induced functional loss during spaceflight that relied on experimental bed rest on Earth, an extreme form of inactivity. However, interest in the primary mechanisms of inactivity was a lower priority.

Today over 6500 publications arise from a PubMed search for the terms spaceflight and physiology. Inspection of this body of literature led Vernikos and Schneider ( 540) to contend that spaceflight results in losses of functional capacities in multiple organ systems, similar to an accelerated model mimicking aging. For example, they conclude that bone atrophy occurs 10-times faster in spaceflight than with aging. Similarly, reductions in immune function, sensitivity of arterial baroreflex, maximal stroke volume, maximal cardiac output, and VO ₂max also occur more rapidly in spaceflight than in aging ( 540, 561). (Cross-reference: Importance of exercise in microgravity)

5.6 Bed rest book (1965)

The preface of Browse's book "The Physiology and Pathology of Bed Rest", published in 1965 states that the principle purpose of the book,

...is to lay bare our ignorance of the whole subject, to stimulate research...The dangers of bed rest are so many, and in some cases so final, that we should always be striving to discard it from our therapeutic armamentarium...and to emphasize the absurdity of using a non-specific treatment for specific diseases without reason or proven value ( 68).

The book carefully documents the widespread systemic deterioration of the body when continuous bed rest occurs. Some of the pathologies documented are: postural hypotension, tachycardia, kidney stones (renal calculi), loss of skeletal muscle mass, weakness in antigravity muscles, pressure ulcers, osteoporosis, constipation, deep vein thrombosis, pulmonary embolism, pneumonia, and difficulty with micturition.

5.7 Dallas Bed Rest Study (1960's)

Saltin, et al. ( 454) studied five healthy college-age males during 20 days of continuous bed rest. During acute exercise following bed rest reductions of 28%, 11%, 26%, and 29% in VO ₂max, ventricular volume (ml), maximal cardiac output, and maximal stroke volume occurred, without a change in maximal A-VO ₂ difference. Further detrimental changes with bed rest were increased heart rate at a submaximal workload of 600 kpm/min from 129 to 154 beats/min and total peripheral resistance (TPR) increasing from 449 to 520 TPR units. From the 10 th-20 th day of bed rest day resting heart rate increased from 47 to 51 beats/min.. (Cross-reference: Cardiac Function; Cardiac output during exercise: contribution of the cardiac, circulatory and respiratory systems)

5.8 Sitting studies (2000's)

Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required...many scientific questions remain to be answered before it can be concluded with a high degree of certainty that these adverse health consequences are uniquely caused by too much sitting, or if what has been observed so far can be accounted for by too little light, moderate, and/or vigorous activity ( 392).

A 2010 review co-authored from multiple research sites concluded from an examination of 43 papers, "Limited evidence was found to support a positive relationship between occupational sitting and health risks. The heterogeneity of study designs, measures, and findings makes it difficult to draw definitive conclusions at this time" ( 537). The concept of intermittency of lack of weight bearing by sitting is supported by older basic science research. In rats cycling 4 times/day through periods of weight bearing and non-weight bearing (hindlimb suspension), soleus muscle atrophy was prevented by 4 × 15-min periods of ground support during 12 hrs of the day ( 118).

5.10 Translation studies - Reduced stepping studies in humans (2000's)

While continuous bed rest is a model examining the absence of physical activity, a novel human reduced-activity model was designed to test the effects of reduced, rather than lack of, physical activity on metabolic health. Step numbers were reduced by taking elevators instead of stairs and riding in cars instead of walking or bicycling within a free-living environment by young, healthy male adults who were not undertaking >2 hrs/wk exercise at the start of the study. After reducing daily step number form 6203 to 1394 for 3 weeks, areas under the curve (AUC) for plasma insulin during an oral glucose tolerance test (OGTT) progressively increased 53%, 61%, and 79% after 1, 2, and 3 weeks, respectively ( 389).

In a second study, subjects reduced daily steps from 10,501 to 1,344 (where there are ~2000 steps in a mile). After 2 weeks, VO ₂max decreased 7%, peripheral insulin sensitivity decreased by 17% with concurrent decreases in insulin-stimulated ratio of pAkt-Thr ³⁰⁸/total Akt in skeletal muscle. Body composition was also significantly altered by 2 weeks of reduced stepping with visceral adipose tissue mass increased 7%, total fat-free mass decreased by 1.2 kg, 0.5 kg of it in the legs, while total-body fat mass and BMI were unchanged ( 286, 389). Thus, an inverse relationship existed between gain of visceral adipose tissue and loss of lean mass, indicative of body composition repartitioning. Similar observations have been made in a rat WL model. In a different WL experiment visceral adipose tissue mass, but not lean mass increased independent of food intake after 173 hours of WL followed 6 weeks of voluntary running ( 310). Thus, both human and rat models of reduced daily steps increased visceral adipose tissue while diminishing lean mass, independent of caloric increases.

5.12 Summary: Inactivity causes loss of functional capacities

Taken together, the historical work provides overwhelming evidence that physical inactivity cause decreases in capacities of functional systems, leading to premature deterioration of health in humans. The Copenhagen study of reduced stepping, while low in subject number, is particularly relevant to everyday living because the reduced physical activity level is similar to the step numbers performed in a free-living environment by billions of humans worldwide in both developed and developing countries.

6. Cause vs. treatment

A sedentary lifestyle over several years is associated with increased risk for type 2 diabetes, cardiovascular disease, and premature mortality. What is much less appreciated is the high cost of physical inactivity even in the short term. Booth et al. have been drawing attention for years to the societal and individual burden of inactivity-related chronic diseases. They remind us that while exercise is a treatment to prevent many chronic diseases, it is the lack of regular exercise or physical inactivity that is one of the actual causes of many of these diseases" ( 481).

Convincing proof that physical inactivity causes primary deterioration of function is provided from extensive historical and scientific evidence. Thus, physical activity can prevent physical inactivity-induced chronic diseases (left panel of Fig 1 ). In contrast (right panel of Fig 1 ), physical activity can treat against lung cancer-induced dyspnea, a common side effect 1 to 6 years after lung cancer resection ( 179) (Right panel Fig. 1 ). Thus, in the left panel physical activity addresses the cause of the disease, while in the right panel physical activity only acts as a treatment against a disease in which it cannot prevent. We will focus on the disease processes of the left panel in this article.

7. Mechanisms of physical inactivity and activity differ

Mechanisms of physical inactivity are considered anti-parallel, rather than in series (continuum) to physical activity ( 210, 570). Physical activity and inactivity reside in different mechanistic planes, and are not merely mirror images of each other as is commonly considered (discussed below). Optimal therapies and preventive strategies require knowledge of causal mechanisms. Thus, it is important to understand that some of the mechanisms by which inactivity causes chronic diseases differ from mechanisms by which exercise acts as primary prevention of same diseases.

One example is that inactivity and exercise differ with regards to time courses of structural changes in conduit arteries and changes in endothelial function. This difference is summarized nicely in a review where Thijssen et al. state: "However, the nature and impact of inactivity and exercise on vascular structure and function suggest that inactivity and exercise are not simply the opposite ends of a linear spectrum of physiological adaptation" ( 506). In our figure 2 , distinct mechanisms by which inactivity and/or exercise alter conduit size and endothelial function are outlined. For instance inactivity results in immediate negative remodeling of the vessel, while activity requires 4-6 weeks to positively remodel the vessel.

A second example that inactivity and exercise are not mirror images of one another is found from global analysis of skeletal muscle gene expression, before bed rest, immediately after bed rest, and after 4 weeks of post-bed rest training. Compared to pre-bed rest levels, 9 days of bed rest altered 4500 mRNAs. If physical activity were merely the reverse of inactivity then all 4500 would be hypothesized to return to pre-bed rest levels following 4 weeks of training. However, a normalization of expression failed to occur in 20% of the 4500 genes that changed with bed rest. This observation led Vaag and co-workers ( 8) to speculate that rather severe and long lasting adverse alterations in mRNA levels may develop in important biological pathways relevant to their general health after 9 days of bed rest.

A third example is by Stein and Bolster ( 491) who compared muscle atrophy ( 311) to skeletal muscle regrowth from atrophy ( 184), and reiterated by Greenhaff and Hargreaves ( 210). Again, if physical activity were the opposite of physical inactivity, then the expected result would be many of the same genes changes would be similar for atrophy and regrowth. However, comparison of these two gene lists showed virtually no common gene names on both lists. These examples illustrate a fundamental principle of biochemistry, which Stein and Bolster concisely state, "This is a common finding in biochemistry. Anabolic and catabolic pathways are usually separate" ( 491)", or put another way, opposite processes work through entirely different mechanisms rather than altering the level of one pathway. Further biochemical examples include; irreversible steps in glycolysis and glycogen synthesis, protein synthesis and degradation, lipolysis and lipogenesis, and mitochondrial biogenesis and mitophagy, all of which support the idea that exercise and inactivity are not merely opposites of each other. Thus, a single molecular paradigm to explain adaptations to exercise and inactivity does not exist.

8. Gene-Exercise/physical inactivity interactions

Physical fitness and physical activity/inactivity interact with genes. While many fitness examples of gene-environment could be chosen, VO ₂ max will be used because it is well studied and integrates the function of multiple organs at multiple levels (i.e. tissue, cell, protein, and gene). (Cross-reference: Genetics: environment and their interaction)

8.1 Genetic Component Alone

Phenotype responsiveness variability to aerobic training

Using untrained pairs of monozygotic twins, dizygotic twins, and brothers approximately 40-50% of VO ₂max was estimated to be due to genetics ( 57). Similarly, pairs of identical twins had significantly more similar increases in VO ₂max than unrelated twin pairs after aerobic training in three papers in the mid-1980s ( 217, 421, 474). The papers led to the milestone paper reporting that some individuals experiencing little or no gain in VO ₂max, whereas others gained >1.0 L/min in 481 sedentary subjects ( 55). A 2.5-times greater variance existed between families than within families in the VO ₂ max response variance.

8.2 Higher VO₂max associates with better health

The 1996 US Surgeon General's Report ( 531) concluded that high CRF decreases the risk of cardiovascular disease (CVD) mortality. High VO ₂max is associated with "positive health"; low VO ₂max is associated with "negative health." Remarkably, low CRF was a stronger predictor of death than clinical variables or established risk factors, such as hypertension, smoking, and diabetes, as well as other exercise-test variables, including ST-segment depression, the peak heart rate, or the development of arrhythmias during exercise in both healthy subjects and those with CVD ( 363). Specifically, subjects aged 60 and older with low CRF had notably higher mortality risk from all causes than those with high CRF ( 499). Maintaining the highest possible VO ₂max is a primary preventer of morbidity and mortality from low VO ₂max (discussed later). Further information on the role of genes, physical activity, VO ₂ max (CRF), and health is presented next.

8.3 Using VO₂max to identify "health" genes

Theoretic selection of specific genes to optimize functional capacities

In 1979, Bennett and Ruben elegantly described a basis for natural selection of genes by physical activity to maximize inherited potential VO ₂ max,

"We believe that this increased stamina and sustainable activity were important selective factors from the outset... The selective advantages of increased activity capacity are not subtle but rather are central to survival and reproduction. An animal with greater stamina has an advantage that is readily comprehensible in selective terms. It can sustain greater levels of pursuit or flight in gathering food or avoiding becoming food. It will be superior in territorial defense or invasion. It will be more successful in courtship and mating" ( 34).

The quotation hints that some genes were selected during evolution to support high levels of physical activity and the ability to adapt to physical activity. However, recent observations that a small portion of the population is low responders for VO ₂ max suggest a greater biological complexity than known in 1979.

Genes associated with plasticity of VO₂max

In 1998, Bouchard and co-investigators published, "Maximal heritability estimates were at least 50%, a value inflated to an undetermined degree by inclusion of nongenetic shared factors" ( 56). Timmons employed a novel approach to improve the examination of complex physiological variables in human models. To identify genes responsible for variance of VO ₂max plasticity, Timmons et al. ( 517) used a novel approach by first conducting mRNA expression microarray profiling, which were then used to produce molecular predictors to locate or rank a discrete number of genes that correlate with the change in VO ₂max following endurance training. Follow up studies allowed for subsequent targeted genotyping and, hence, discovery of key genetic variants responsible for the variance of VO ₂max plasticity. A signature of 29 mRNAs and of 11 single nucleotide polymorphisms (SNPs) were identified that predicted ~50% and ~23%, respectively, of the estimated variance for VO ₂max plasticity following aerobic training in humans ( 517). Timmons et al. ( 517) noted two remarkable characteristics in their identified 29 predictor mRNAs: 1) pretraining levels were greater in high than low responders for VO ₂max; and 2) >90% of the 29 mRNAs did not change with aerobic training. They suggested that individuals with a low responder predictor gene profile would require alternative exercise intervention paradigms or more intensive pharmacological and dietary protocols to help compensate for their genomic profile. Timmons and co-authors further examined the same subjects after 6 weeks of endurance training at 70% of maximal VO ₂max ( 517). They observed that low-responders did not switch on their proangiogenic network genes effectively ( 269). (Cross-references: Molecular mechanisms and muscle plasticity with acute and chronic exercise; Muscle plasticity: energy demand and supply processes; Regulation of gene expression in skeletal muscle by contractile activity).

Timmons et al.'s ( 517) development and validation of mRNA predictors to hunt for genetic markers have many advantages over existing approaches of SNP. Each SNP seems to contribute only weakly for chronic complex human diseases. For example, after genome-wide association analysis in type 2 diabetes (T2D) patients, 18 robust SNPs explain <7% of the total disease variance ( 484). As to generalization of a low responder to all of tens of health benefits from exercise training from VO ₂max alone, Timmons cautions, "No systematic analysis allows us to be certain that a `nonresponder' for one trait does not cluster with a poor response for another" ( 516). Thus, additional research is needed to determine whether low responders for gain in VO ₂max with endurance training respond to other "positive health" benefits of physical activity, such as improved cognitive function, bone density, skeletal muscle strength, visceral adipose tissue quantity and quality, and the tens of other "positive health" benefits detailed later in this article ( 52). Blair, Church, and co-workers ( 478) reported that non-responders to for increase in VO ₂ max comprised a total of 44.9%, 23.8%, and 19.3% of the 4-, the 8-, and the 12-kcal/kg/wk treatment groups, respectively. They concluded that greater volumes of exercise were associated with a lower probability of being a nonresponder. In summary then, additional research is needed to determine if low responders to aerobic exercise are low or high responders to high-intensity interval training, to resistance training, balance, or flexibility training.

Proof due to experimental selection of physical aerobic-fitness genes in animals

Britton and Koch's experimental selection, based upon a single volitional/behavioral forced running test to exhaustion, provided experimental evidence that natural selection for high aerobic capacity during evolution is a feasible concept ( 569). Selection of rats on the basis of the longest or shortest running distances during a single exercise test resulted in selection of a 58% higher aerobic capacity in the high-distance line than the short-distance line over 11 generations. Rats with high VO ₂max had healthier cardiovascular systems (12% lower mean 24-hr blood pressures and 48% better acetylcholine-induced vasorelaxation), and healthier metabolic risk factors (16% less fasting plasma glucose, 39% less visceral adipose tissue, 63% lower plasma triglyceride levels, and greater mitochondrial protein concentrations). These data provides evidence of a genetic role in inter-animal variation in VO ₂ max that is correlated with better health outcomes.

8.4 Phenotype responsiveness variability to resistance training (RT)

In addition to VO ₂max variance among subjects in response to aerobic training, RT also has a tremendous amount of variability in adaptive responsiveness. In 585 subjects undergoing 12 weeks of RT, changes from 2 to +59%, 0 to +250%, and −32 to +149% occurred in cross sectional area, one repetition max, and maximal isometric contraction, respectively ( 250). The variability in muscle mass may, in part, be related (but not limited) to inter-individual differences in genome code (as with IGF2 in the aforementioned porcine model) ( 377), the individual's ability to activate intramuscular mTORC1 signaling within skeletal muscle in response to exercise ( 333), and/or different responses of microRNA (miRNA) to RT( 120). Successful RT-induced hypertrophy in human skeletal muscle was associated with specific differences in miRNA expression to RT in high- and low- responders, respectively, which Davidsen et al. ( 120) suggest means that miRNAs may play a role in regulating the translation of key gene networks responsible for human skeletal muscle growth. One possible pathway is the PI3K/Akt/mTOR pathway, which is up-regulated during skeletal muscle hypertrophy in humans, and related to the ability for satellite cells to proliferate and/or differentiate ( 411).

8.6 The future of personalized human medicine

The findings of the previous sections have led Timmons et al. ( 517) to predict that they could apply gene data for changes in VO ₂max in personalized medicine to tailor exercise prescription. Medicine will continue to become more personalized with the looming question of how to optimize how it is applied to ensure the greatest patient benefit. Carl Sagan wrote, "It is the tension between creativity and skepticism that has produced the stunning and unexpected findings of science" ( 452). It is the spirit of Sagan's quotation that we now raise issues about which we are skeptical. We are skeptical that exercise experts will be used to inform health care professionals on how to make personalized exercise prescriptions based on science. The fear is that a patient will be informed that they have low-responder genes for VO ₂ max, which may lead to failure of the patient to exercise or lack of compliance to alternative exercise prescriptions. We hope that solutions, such as encouraging low responders to aerobic exercise or to engage in resistance exercise, can lead to striking improvements in personalized health.

8.7 Clinical significance

In a statement in Science, NIH Director Francis Collins wrote,

However, the best opportunity to reduce risk in genetically susceptible people for the foreseeable future will not be to re-engineer their genes, but to modify their environment. We need to understand how genetic factors and environmental exposures interact in individuals to alter normal biological function and to affect the risk of disease development ( 464).

The clinical significance of low- and high-responders for a given dosage and type of exercise, implies that individualized medicine, if exclusively restricted to viewing genetic background in vacuum, will result in less than optimal prescriptive therapy. Rather, individualized medicine for primary prevention of disease and premature death must also be based on individualized variation of inherited genes for: a) disease susceptibility, b) responsiveness to exercise training and type of exercise, and c) drug-exercise interactions, if appropriate. Thus, fully capturing personalized gene-environment interactions.

Kujala et al. ( 289) wrote, "When tailoring clinical physical activity interventions, we must remember that not all individuals are suited to the same guidelines for exercise intensity, because the ability to exercise seems to vary not only by training background but also by genetic predisposition."

9. Twin studies - Modulation of twin phenotype by physical activity

Claude Bouchard has extensively used the experimental approach of MZ twins to minimize genetic variability for estimating the percentage contribution of environmental (physical activity) interventions since the mid-1980s. In addition to studies where twins were subjected to exquisitely controlled exercise protocols, a number of studies used overfeeding protocols to look at the effect of excess calories (not included in the following tables). The twin approaches have been critical to our ability to separate genetic from environmental effects related to health and chronic disease in humans. Future, twin-activity studies will contribute to prescription of exercise types and of dose-response thresholds for primary prevention of chronic diseases.

9.1 Comprehensive presentation of twin-activity (gene-environment) studies

In this section, we take the approach of searching the literature for all articles (that we could find) that have examined a variety of health outcomes in monozygotic twins (MZ) to attempt to control for genetic variation.

9.2 MZ twin-activity comparisons show high mortality component

To summarize the most important health outcome, mortality, Table 2 is presented to show the mortality outcome in MZ twins discordant for physical activity in a large cohort of Swedish twins ( 77). The higher physically active MZ had a 36%-66% lower mortality than their inactive MZ pair.

Table 2

Sex

Physical activity level

All-cause mortality

Cardiovascular mortality

Hazard ratio

95% confidence intervals

Hazard ratio

95% confidence intervals

Men

Low

1

1

Women

Low

1

1

9.3 MZ twin activity comparisons show variable chronic disease component

These studies have taken the approach of either a priori separating pairs of MZ that are discordant for physical activity ( Table 3 ), looking at exercise responses in MZ twins relative to dizygotic twins ( Table 4 ), correlating health parameters with physical activity or fitness levels in MZ twins ( Table 5 ), and looking at the genetic component of physical fitness and activity parameters ( Table 6 ). By evaluating this approach, we can obtain an idea about which factors are controlled mainly by genetics and which are most modifiable for physical activity levels. However, it should be noted that many of these studies have methodological limitations including a wide range of physical activity levels and outcomes that differ from classical exercise physiology adaptations.

Table 3

Outcomes

Physical Inactivity Effect

MZ (n)

Other (n)

Sex

PA Measurement

Comments

Ref

MRI Liver Fat Score

↑ 170% in inactive Twin

MRI Intramuscular Fat

↑ 54% in Inactive Twin

WC changes from 1975 to 2005

↑ 8.4 cm in inactive twin

Waist Circumference

↑ 8.4 cm in inactive twin

HDL

↓0.14 in inactive (p=0.004)

HDL2

↑ 2.71 in inactive (p=0.001)

Apo A-1

↑ 0.10 in inactive (p=0.004)

aBMC

↓ Sig in inactive twin

Life Happiness

N.S.

VO2max

E is 35% & G is 45%

Total Body Fat

E is 20% & G is 70%

Endothelial function via ultrasound of brachial and LAD coronary artery

N.S.

Oxygen extraction fraction

↑ in low fit (p=0.06)

Myocardial FFA uptake at rest and during exercise

N.S.

Right-side hypertrophy index

LV mass index

Mortality from 1975-1981

↑Sig in inactive DZ twins, but not inactive MZ twins

157

517

B

Questionnaires for vigorous PA and estimates of >2MET wk/day/wk

Finnish twin cohort aged 24-60. Low level of leisure physical activity in early life was associated with increased risks of death in dizygotic twin pairs, but monozygotic co-twins.

( 289, 546)

Table 4

PA Intervention

Outcomes

H-effect

MZ (n)

DZ (n)

Sex

Comments

Ref

LV diameter (rest)

N.S

Fractional shortening (rest)

H = 13% (N.S)

Change in End-diastolic mean wall thickness w/exercise

H = 0% (N.S.)

Change LV diameter w/exercise

H = 24%

Change in Fractional shortening w/exercise

H = 47%

Cycling Power output

H = 53%

Cycling VO2max

H = 46%

DBP (rest)

Change in SBP w/exercise

Change in DBP w/exercise

O2 uptake at HR of 150bpm

H = 61%, 16% when PA and skinfolds adjusted

Mechanical Efficiency

N.S. H Correlation

Anaerobic energy generation

H = 78%, 58% when PA and skinfolds adjusted

Respiratory exchange ratio

H = 6% only

ACTH and cortisol response to exercise and beta-endorphin at rest

N.S. H Correlation

Fasting and postprandial insulin

dehydroepiandrosterone sulfate & androsterone glucuronide

Sig. H effect

7

M

Healthy Young Males.

( 419)

Cortisol levels

Max Lactate Wingate

H = 82%

Delta Lactate during maximal test

H = 84%

oxoglutarate dehydrogenase activity (OGDH)

Sig H

VO2 max

N.S. H Correlation

Maximal lactate

H = 75%

fiber-type, CK activitiy,

N.S. H

fiber type & anaerobic capacity

Rest v Ex LV internal diameter

N.S. H

Rest v Ex Fractional Shortening

N.S. H

LV Mass

N.S. H when adjusted for BW

Change in fasting TAGs and Cholesterol

Change in VO2max, RER during exercise

Pre v Post delta insulin during OGTT

N.S. H

basal lipogenesis

Sig H

Pre v Post insulin stimulated lipogenesis

N.S. H

Pre v Post epinephrine and basal lipolysis

N.S. H

Pre v Post LPL activity

N.S. H

Fat Free Mass

Sig H

Basal lipolysis

N.S. H

LDL Cholesterol

HDL Cholesterol

LDL Cholesterol

Cholesterol to HDL ratio

Baseline thermic effect of food

Thyroid hormones

Table 5

Outcomes

H-effect

PA Effect

MZ (n)

DZ(n)

Sex

PA Measurement

Comments

Ref

BMI

N.S.

waist circumference

46%

leg BMC

↓ 1.4% in inactive

Spine BMC

↓ Sig in inactive

Table 6

PA Measurement

H-effect

Unique Environmental Effect (unless noted)

MZ (n)

DZ (n)

Sex

Comments

Ref

Respiration chamber (doubly labeled H ₂ O) activity-induced energy expenditure

8%

30%

12

8

B

Aged 17-39 yr old. Univariate analysis using the additive genetic, but excluding the common environmental component.

( 259)

Doubly labeled H ₂ OFree living activity induced energy expenditure

72%

29%

Total EE by Doubly labeled H ₂ O

19%

23%

Skeletal muscle mitochondrial activities

N.S.

Oxidative to glycolytic ratio

25-50%

As expected many of the tested health parameters had both genetic and environmental components. In many studies, questionnaires were used to evaluate physical activity levels, a less than optimal method to collect such data. Thus, while the design of the studies analyzed was not optimized for elucidating the effects of physical activity independent of genotype, some cautious conclusions may be made from Tables 2 - 6 , presented next.

9.6 Clinical significance

Taken together, data in Tables 2 - 6 provide conclusive evidence that physical inactivity alone is sufficient to increase chronic diseases and death. "Together, the 80 monozygotic publications unequivocally show that co-twins with lower physical activity levels exhibit increased risks for chronic diseases regardless of genotype. Such data, therefore, empowers physicians and other health care providers to prescribe physical activity as primary preventative medicine"

10. Variety of training types to primarily prevent disease

Specificity of training (i.e., adaptation to training is specific to the class of exercise (aerobic vs. resistance) is dogma. For example in 1976, one of us wrote that the nature of the exercise stimulus determines the type of adaptation ( 243). One type of adaptation involves hypertrophy of the muscle cells with an increase in strength; it is exemplified in its most extreme form by the muscles of weight lifters and body builders. The second type of adaptation involves an increase in the capacity of muscle for aerobic metabolism with an increase in endurance and is found in its most highly developed form in the muscles of competitive middle- and long-distance runners, long-distance cross-country skiers, bicyclists, and swimmers. Further, hypertrophied muscles of weight lifters did not have the increased mitochondria of aerobic training and that prolonged daily run training increases mitochondria, but does not hypertrophy the muscles. Application of the information to elderly individuals is that they must perform both types of exercise to prevent physical (endurance and strength) frailty.

Recent information expands and emphasizes the specificity dogma. High-intensity interval training (HIT) (near peak performance for short bursts alternating with longer periods of low-intensity aerobic activity) has been said to "prove more benefit than traditional continuous exercise programs in several metabolic, muscular, and cardiovascular parameters" ( 278). For example, HIT-walking resulted in greater increases in VO ₂peak and thigh muscle strength and a greater reduction in SBP than moderate-intensity continuous walking in older men and women ( 375). In contrast, one HIT report indicates that HIT by untrained men produced greater (VO ₂max), the same (improvements in oral glucose tolerance), and less (resting bradycardia, total-body fat percentage, and reducing ratio between total and HDL plasma cholesterol.) adaptations than in a second group performing continuous training ( 384).

11. Diseasome of physical inactivity (35 diseases/conditions)

The term "diseasome of physical inactivity" was presented by Pedersen ( 403) to describe a clustering of diseases. Our article enlarges Pedersen's cluster to include over 35 diseases/conditions and death, which constitute most of the remaining article ( Fig. 3 ). (Cross-reference: Muscle as an endocrine organ) Joyner and Pedersen ( 260) contend that it is a failure of regulation at multiple levels that causes many common diseases. They further argue that a lack of fluency to use key physiological concepts (like homeostasis, regulated systems and redundancy) as major intellectual tools to understand at multiple levels how whole animals adapt to exercise and maladapt to physical inactivity.

12. Inactivity accelerates loss of functional capacities with years of life

12.1 Definitions

Functional capacity

Absolute maximal value of a function

Relative functional capacity Relative age of functional capacity of an organ system, an organ, or cell to its lifetime highest value at a given calendar age

12.2 Etiology

Primary prevention

The next quotation is impactful because of its source, a report from top exercise scientists that was accepted by the top official of the U.S. Department of Health and Human Services.

The data very strongly support an inverse association between physical activity and all-cause mortality. Active individuals - both men and women - have approximately a 30% lower risk of dying during follow-up, compared with inactive individuals. This inverse association has been observed among persons residing in the United States, as well as in other countries, older persons (aged 65 years and older), and persons of different race/ethnic groups. In one study of persons with impaired mobility (unable to walk 2 km and climb 1 flight with no difficulty), physical activity also appeared to be associated with lower all-cause mortality rates. ( 412)

Less physical activity shortens years of life relative to average lifespan

Another example of lifetime physical activity shortening years lived is the increased risk of chronic diseases such as type 2 diabetes (See type 2 diabetes later in article). Diagnosis of type 2 diabetes at the age of 20 yrs is associated with 17.2 and 17.9 yrs of life lost in males and females, respectively ( 366).

12.3 Dose-response relationship between sitting time and prediction of premature death

Mechanisms

While light physical activity is associated with rather low-intensity muscle contractions, it still has favorable improvements on plasma glucose in glucose tolerance tests ( 228), and differs substantially from the absence of muscle activity while sitting The detrimental effects of sitting have been hypothesized by Stamatakis et al. ( 489) to occur in the following sequence of events: excessive sitting lowers skeletal muscle blood flow, lowering shear stress on vascular endothelial cells,,and decreasing endothelial nitric oxide synthase (NOS) expression. They also noted that the low-grade inflammatory marker, CRP was approximately 2 times greater in subjects with >4 hr/day in screen time, compared to those <2 hr/day. However, two weeks of reduced daily stepping ( 286) and 5 days of bed rest ( 216) do not increase inflammatory markers so CRP is unlikely to be the first initiating mechanism. Rapid biochemical changes in a rodent models of sitting, hindlimb unloading, have demonstrated decreases in rat skeletal muscle protein synthesis rates within the first 6 hrs ( 54, 357, 507, 529, 550) and loss of insulin-stimulated glucose uptake into the mouse soleus muscle after 1 day ( 466).

12.4 Biomarkers of premature death

Low values of functional capacities for maximal aerobic capacity (VO ₂ max) and for maximal skeletal muscle mass/strength, each alone, are biomarkers for death as they are associated with shorter life expectancies.

Sedentary lifestyle speeds secondary aging of VO₂max by 30 yrs (illustrated by shifting of age-VO2max relationship leftward in shown example)

As previously discussed, VO ₂max is a measure of CRF. CRF is a health-related component of physical fitness defined as the ability of the circulatory, respiratory, and muscular systems to supply oxygen during sustained physical activity. While physically active and inactive individuals lose a VO₂max at a similar rate (slope of the curve) due to primary aging, the inactive individuals have a leftward shift of the curve. For instance, 80-yr-old, physically active women had VO ₂max's that were equivalent to 50-yr-old physically inactive women. ( Fig. 4 ) ( 503).

Low VO₂max increases prevalence of death

An inverse relationship between CRF and death was present with a cross-sectional comparison between lesser fit men and women with greater fit men and women showed. When CRF in the second lowest CRF quintile is compared to the lowest quantile, the risk of all-cause death in the lowest CRF quantile is increased by 39% and 67% in a prospective study of 40,451 men and 12,831 women, respectively ( 312) ( Fig. 5 ). Likewise comparing the highest CRF quintile) to the second lowest increased all-cause death risk by 26% and 28% in men and women, respectively. Thus, comparing the top quintile to the lowest quintile increased all-cause death risk by 75% and 113% in men and women, respectively.

Sedentary lifestyle speeds secondary aging of skeletal muscle power by 24 yrs (illustrated by shifting of age-power relationship leftward in shown example)

Low muscle strength has been inversely associated with all-cause-mortality in thirteen studies using subjects > 65 yrs of age (see ( 451) for refs). While, aging causes a similar rate of loss in power between 40 and 90 yrs of age, untrained, healthy men generate 35% less average power than male competitors at a World Masters Weight-Lifting Championships ( 402) ( Fig. 6 ). Recreational resistance training results in strength gains ranging from 10%-257% after 9-52 weeks of 2-3 days/week resistance training in subjects mainly aged between 60-80 years of age ( 252), however a cross-sectional study spanning 20-80 yrs of age in recreational weight-lifters is not available to our knowledge. (Cross-references: Influence of exercise on protein and amino acid metabolism; Physical activity and skeletal muscle size)

12.5 Mechanisms

Evolutionary origin

Maximal functional capacity defines the upper limit of a cell, tissue, system, or whole body to maintain homeostasis to stress. Hayflick ( 226) and others argue that greater functional capacity in vital organs ensures survival, reproductive success, and thus is favored by natural selection. Hayflick lists some stresses that higher capacities in organ systems would be more likely to favor natural selection as

...more efficient healing process, faster sensory responses, or greater strength or speed to avoid predation or natural disasters, finding food, and surviving disease, accidents, and environmental extremes. The favored animals will have developed redundant capacity, or greater physiological reserve, thus increasing chances for survival to reproductive success. ( 226)

In an extreme stress, such as needing maximal caloric expenditure (reflected in VO ₂ max) or skeletal muscle strength, animals whose vital systems have the largest redundant functional-capacity would be better able to survive the stress. Thus, the ability to adapt to and develop greater physiological capacity in response to repeated stressors (i.e. physical activity) was likely a consequence of natural selection.

12.6 Clinical significance

Low CRF (VO ₂max) and handgrip strength predict the risk of impending death. To minimize the all-cause death risk, lifelong efforts, starting in youth, are needed to develop high CRF and skeletal muscle strength within the limitations of one's inherited genes. Slowing of secondary aging of CRF and strength functional capacities can delay the age for inevitable threshold of frailty due to primary aging. A more detailed coverage of inactivity and aging is given in our review ( 50).

13. Prevention of death by primary prevention of physical inactivity

13.1 Etiology

Blair et al. ( 45) first showed in 1989 that an asymptote exists between metabolic equivalents (METs) and age-adjusted mortality rates. Mortality was independent of MET values > ~9 METs in women and >~10 METs in men, but increased when lower than these values.

Kokkinos and Myers found an identical trend in 15,000 older veterans ( Fig. 7 ) ( 278). An age-related threshold for mortality risk reduction at 4 to 6 METs and an asymptote occurred at ~9 METs for women and ~10 METs for men (MET values are multiples of resting metabolic rate).

Figure 7 , shows 20% increase in mortality exists for an individual when maximal exercise MET values grouped between 4.1-6.0 METs fall into 2.1-4.0 MET group, with no further increase between groupings of MET values <2.0 METs and 2.1- 4.0 METs ( 278). This suggests that a threshold at around 4.0 METs below which, no further increase in mortality exists. Further, an asymptote around 9.0-10.0 METs indicates that no differences in mortality risk were reported in comparisons among the higher MET ranges of 10.1-12.0, 12.1-14.0, and >14.0.

Cautionary statements are necessary though. Maximal MET values decrease ~10%/decade with aging, in part due to decreased physical activity levels. Thus, physical activity levels need to be maintained or increased to remain in or near to the asymptotic region (>9 METs) as long as possible with aging..

13.2 Clinical significance

Primary prevention of death (shortening of life expectancy) is possible by increasing CRF.

14. Metabolic syndrome (MS)

All risk factors for MS are exasperated by sedentary lifestyle ( Fig. 8 ). In other words, physical inactivity is a primary cause of MS risk factors by virtue of its being upstream to the common MS risk factors. Alternatively, risk factors for MS are secondary to sedentary lifestyle. Consequently, increased physical activity is primary prevention of MS. (Cross-reference: Metabolic syndrome: Impact of lifestyle)

14.1 Disease definition

MS is currently defined as a cluster of three of five risk factors for CVD and type 2 diabetes, which tend to cluster together in the same individual ( Fig. 8 ) ( 6). Four of the five factors have drug treatments in attempts to normalize them, and include elevated triglycerides, reduced HDL-cholesterol, elevated blood pressure, and elevated fasting glucose. The fifth factor, elevated waist circumference (as a marker of elevated visceral obesity) does not have as an effective drug treatment. Three abnormal findings out of the five risk factors indicate that an individual has MS. In addition, MS is associated with increased risk of certain forms of cancer, polycystic ovarian disease, nonalcoholic fatty liver disease, and neurodegeneration ( 39).

14.2 Etiology

The total number of U.S. adults who have MS ranges from 77-86 million (34.3%-38.5% of total age-group) ( 187). A Joint Scientific Statement indicates that patients with MS have twice the risk of developing CVD and type 2 diabetes, respectively, over the next 5 to 10 years, as compared to individuals without MS ( 6). Physical inactivity has been shown to be an important risk factor of MS ( 38, 186, 296, 560). The proportion of sedentary time, determined by accelerometry was strongly related to metabolic risk, independent of physical activity ( 22).

14.3 Mechanisms

A 2009 Joint Scientific Statement from the American Heart Association states, "Most persons with the metabolic syndrome have abdominal obesity and insulin resistance. Both of the latter conditions appear to contribute to the development of metabolic risk factors, although the mechanisms underlying these contributions are not fully understood ( 6)." However, it is understood that physical inactivity is a primary causal mechanism of every MS risk factor - dyslipidemia, hypertension, hyperglycemia, visceral obesity, prothrombsis, and pro-inflammatory events ( Fig 8 ).

15. Presentation strategy for diseases composing MS

Each risk factor for MS and chronic diseases resulting from MS will be individually considered next.

16. Obesity

16.1 Disease definition

The CDC defines overweight for adults as BMIs of 25.0-29.9; obese class I as 30.0-34.9 BMI; obese class II of 35.0-39.9 BMI; and obese class III >40.0 BMI. A future auxiliary definition will likely include waist circumference as a proxy for intra-abdominal adipose tissue since all fat is not equally unhealthy.

Etiology 45% of the U.S. adult population was estimated to be overweight or obese in 1960-1962. Overweight and obesity began a continual rise in U.S. adults, aged 20-74 yrs, in the 1980's. The percentage of overweight and obese were 45%, 47%, 56%, 65% and 66% in survey years 1960-62, 1976-80, 1988-94, 1999-2000, and 2003-04, respectively, with men ~10% higher than women ( 87, 387); ( Fig. 9 ). A recent publication establishes that 68% of U.S. adults in 2007-2008 are overweight and obese ( 182).

16.2 Misconception that obesity is independent of physical inactivity

The next sections document historical declines in physical activity, putatively reflecting increases physical inactivity.

16.3 Caloric expenditure from physical activity has decreased historically

Caloric expenditure of modern day hunter-gatherers and U.S. Amish vs. sedentary

The modern hunter-gatherers' daily estimated energy expenditures for physical activity are at least 600 kcal more than the average U.S. sedentary adult of today, as documented in column labeled "EE PA" ( Table 7 ) ( 385). The authors of the data in Table 7 commented, "The systematic displacement from a very physically active lifestyle in our natural outdoor environment to a sedentary, indoor lifestyle is at the root of many of the ubiquitous chronic diseases that are endemic in our culture" ( 60). Astrand and Rodahl have made a similar comment,

Close to 100 percent of the biologic existence of our species has been dominated by outdoor activity. Hunting and foraging for food and other necessities in the wilds have been a condition of human life for millions of years...there is obviously no way to revert to our natural way of life...but with insight into our biological heritage we may yet be able to modify our current life, Knowledge of the function of the body at rest, as well as during exercise under various conditions is important as a basis for an optimization of our existence" ( 17).

Table 7 shows that agrarian Amish men and women undertake 900 and 700 calories worth of daily physical activity, ( 439). They eat a typical American dieting terms of macronutrients consisting of meat, potatoes, gravy, cakes, pies, and eggs ( 439). Nonetheless, only 25% and 27% of these Amish men and women, respectively, are overweight; and 0% and 9%, respectively, are obese ( 439). Several simple observations give rise to conclusions that the lower physical activity levels of modern inactive humans contributes to the obesity epidemic more so than an increase in caloric intake. Agrarian Amish physical activity expenditures exceed modern sedentary by at least 600 kcal/day ( Table 7 ). If modern caloric intake remained unchanged then on average each individual would have a positive energy resulting in 73 pounds of fat/year. Clearly this is untrue and therfore caloric intake must have dropped. However, if the modern population had a decrease in caloric intake of more than 600 kcal/day then obesity rates between Amish and the general population would be similar, which is also untrue. Thus, while caloric intake has dropped between 0 and 600 kcal/day in the general population it is the lack of 600 kcal/day of physical activity has led to a large discrepancy in the obesity rates between the modern general population and Amish societies.

Modern human caloric expenditure is less than free-ranging mammals

Compared to other free-ranging mammals, Hayes et al. ( 225) calculate that sedentary humans have a significantly lower level of relative physical activity-induced energy expenditure. However, highly active humans have relative physical activity-induced energy expenditure that nears that of other free-ranging mammals ( Fig. 10 ).

Decreases by physical activity type in past few decades: China

James ( 256) shows that transfer from working in the field in China to city work would drop caloric expenditure by ~315 kcal/day (men) and ~375 kcal/day (women). James comments,

...these calculations are set out to illustrate how foolish it is to focus on only one of the two parts of the energy balance equation. The calculations also illustrate the magnitude of the required drop in intake, given the transformation in our working conditions" ( 256).

Further, instead of walking to fields, motorized transportation is taken, reducing caloric expenditure by an additional ~200 kcal/day. James concludes,

"Thus, intakes may need to fall by 400-800 kcal/day for each Chinese adult as their working and living conditions change, and the physical revolution transforms working conditions and transport, with city living and home entertainment with television and cinema viewing taking over from the major sustained demands of an agricultural life" ( 256).

The misconception of "overnutrition" is due to a widening positive caloric balance due to food intake not falling calorie with calorie to the decline in caloric expenditure (PubMed cites >100,000 papers with the term "overnutrition").

Caloric cost of engineering physical activity out of lifestyle

Energy expenditure was significantly greater when daily domestic tasks were performed without the aid of machines or equipment. An estimated 110 kcal/d was estimated to be expended by the combined impact of domestic mechanization ( 304) ( Table 8 ). The annualization of 110 kcal/day is the caloric equivalent of 11.5 pounds of fat/yr. Levine and co-authors concluded, "the magnitude of the energetic impact of the mechanized tasks we studied was sufficiently great to contribute to the positive energy balance associated with weight gain" ( 304).

We followed Levine's model and calculated an annualized loss of 64,349 calories (caloric equivalent of 18.4 pounds of fat in one year) would not be expended when walking/standing is selected out of lifestyle in our hypothetical model ( Table 9 ).

Alternative interpretation that physical activity has not declined

Westerterp concluded,

"Physical activity energy expenditure, as measured with doubly labeled water (DLW), has not declined since the start of the obesity epidemic in the 1980s ( 554)... it is unlikely that decreased expenditure has fuelled the obesity epidemic."

Our view of the above quotation follows. Indeed, DLW estimates of energy expenditure determined between 1988 ( 555) and 2006 ( 554) did not significantly differ. However, from ~1980 to 1988 the increased prevalence of obesity was already occurring and the slope of the increase remained unchanged through 2006 ( Fig. 9 ). The unchanged slope suggests that whatever was responsible for the increasing prevalence of obesity was maintained, not increased or decreased through 2006. Thus, physical activity levels may have been altered downward prior to 1988 and maintained from 1988-2006 at their low levels, which could be one possible explanation for the inconsistency between the DLW results and lack of change in physical activity levels

16.4 Primary prevention of total-body fat gain by physical activity

It is preferable to avoid, in the first place, the excess weight gain that leads to overweight and then obesity...A major emphasis on obesity prevention is needed in the population at large to prevent the development of obesity in those adults who are still in the normal weight range and in successive generations of children and adolescents during development. Treatment will continue to be of critical importance, but treatment alone cannot curb the epidemic...prevention has not been the primary focus ( 292).

Mimimal research exists on preventing weight gain.

Primary prevention is demonstrated by one human study. A threshold of ~60 minutes a day of moderate-intensity activity throughout a 13-yr study was needed to gain <2.3 kg in 34,079 healthy US women consuming a usual diet. In a 3-yr sub-study, the only group having significantly less weight gain than other groups was women whom fit all 3 of the next criteria: BMI < 25, moderate-intensity exercise >60 min/day, and < 64 yrs of age ( 314).

Primary prevention of further weight gain in already overweight to obese individuals was accomplished with 8 months of low volume-moderate intensity activity (caloric equivalent of walking 12 miles/wk at 40-55% of VO ₂max), while high-volume (caloric equivalent of jogging 20 miles/wk at 65-80% of VO ₂max) decreased total fat mass by 4.8 kg ( 480)

Primary prevention of weight regain was calculated retrospectively, after 12 months in previously obese female, to be 80 min/day of moderate activity, 35 min/day of vigorous activity, or 0.011 kcal physical expenditure/kg body weight/day ( 461). Maintenance of a 10% reduced body weight in humans with BMIs >30 is associated with a significant decrease in total energy expenditure of ~300-500 kcal/day greater than that predicted by changes in body mass and composition, which is due predominantly to increased work efficiency of skeletal muscle at low work intensities ( 203).

Joyner and Pedersen ( 260) present another example. Low prevalence of obesity has been related to poor economic conditions. Collapse of the Soviet empire in at the end of the 1980s led to decreased food availability, increased physical activity and ~50% decrease in adult obesity prevalence in Cuba ( 441). Upon economic recovery, obesity rose 50% from 1993 to 1996.

16.5 Preferential decrease in visceral adipose tissue (VAT) by exercise

Primary prevention of VAT obesity by physical activity has been demonstrated in numerous human studies. Physical training of T2D patients produced a greater loss in VAT (48%) than subcutaneous adipose tissue (SAT) (18%), did not significantly affect body weight ( 360). Ross et al. ( 447) reported that exercise without weight change in obese men reduced VAT more than SAT. Likewise, a greater percentage loss in VAT percentage than in body weight occurred after 12 months in a moderate-intensity exercise intervention study of sedentary, overweight, postmenopausal women. VAT loss was exercise dose-dependent ( 253).

A 6-month study examined the dose-response relationship for exercise volume-VAT mass in men and women whose BMI's ranged from 25-35 ( 479). Low volume-moderate intensity (caloric equivalent of walking 12 miles/wk at 40-55% of VO ₂max) was sufficient to prevent any further gains in VAT mass, while high-volume, high-intensity activity decreased VAT by 6.9% ( Fig. 11 ).

Remarkably, the non-treatment group (no exercise) had an 8.6% increase in VAT. Extrapolated to 10 years, this would have been a 172% increase in VAT. Kraus et al. ( 482) later wrote about the non-exercise group, "current levels of physical activity may be so low that significant metabolic deterioration occurs in numerous health-related parameters in as little as 6 months of continued inactivity." The study provides the evidence that a primary cause of VAT obesity is lack of exercise and that primary prevention for the expansion of VAT is physical activity ( Fig. 1 ).

16.6 Primary prevention of inactivity prevents obesity with predisposed obesity gene

Sedentary lifestyle reveals an obesity phenotype that is primarily prevented by enhanced physical activity.

Humans

The 16% of sedentary adults who are homozygous for the risk allele of AA in rs9939609 in the fat mass and obesity-associated (FTO) gene weighed ~3 kg more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele ( 191). Physically inactive homozygous risk A-allele in rs9939609 carriers had a 2 kg/m ² greater BMI compared with homozygous T-allele carriers in a cross-sectional study of 17,000 Danes ( 14). A second study replicated the primary preventative effect of physical activity. Adolescents meeting the daily physical activity recommendations overcame the effect of the FTO rs9939609 AA polymorphism on obesity-related BMI, body fat, and waist circumference traits seen in sedentary subjects ( 450). High physical activity levels in additional studies were associated with attenuated BMI and waist-circumference obesity traits for two additional FTO polymorphisms [rs1861868 ( 422) and rs1121980 ( 543)]. Women with the FTO allele rs8050136 only have obesity risk if they are less active ( 5). In summary then, physical inactivity is required to elicit the phenotype of obesity with polymorphisms predisposing to obesity for the human FTO gene.

16.7 Mechanisms

Physical inactivity, as one of the two components in the caloric balance equation, is an actual cause of positive caloric balance, i.e., obesity. The most effective control of obesity is primary prevention of physical inactivity by moderate levels of physical activity, rather than secondary or tertiary prevention of obesity associated co-morbidities.

17. Inactivity fosters obese co-morbidities

17.1 Obesity co-morbidities

Risks for the following conditions increase with physical inactivity: Coronary heart disease, T2D, cancers (endometrial, breast, and colon), hypertension, dyslipidemia (for example, high total cholesterol or high levels of triglycerides), stroke, liver and gallbladder disease, sleep apnea and respiratory problems, osteoarthritis, and gynecological problems (abnormal menses, infertility).

17.2 Clinical significance

Physical inactivity is a cause of some obesity co-morbidities. Thus, even if primary prevention for the loss in body fat fails, primary prevention of some, but not all, of obesity's co-morbidities is possible with physical activity.

18. Insulin sensitivity/resistance

18.2 Insulin sensitivity

How successful blood glucose is lowered by blood insulin

18.3 Insulin resistance

Diminished ability of skeletal muscle and liver cells to respond to the action of a given dose of insulin by transporting glucose from the bloodstream into these tissues, or by reducing glucose production, respectively (B to D in Fig. 12 )

A hyperbolic relationship between insulin sensitivity and insulin secretion has been defined as by Bergman ( 36). Fig. 12 illustrates the progression from normal glucose tolerance (Point A) to overt clinical T2D (Point D), as described in Harrison's textbook,

glucose tolerance remains to near-normal (NGT), despite insulin resistance, because the pancreatic beta cells compensate by increasing insulin output (Points A to B). As insulin resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain individuals are unable to sustain the hyperinsulinemic state. Impaired glucose tolerance, characterized by elevations in postprandial glucose, then develops (Points B to C). A further decline in insulin secretion and an increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemia (Point D). Ultimately, beta cell failure may ensue ( 418).

We have further modified Harrisons' redrawing of Bergman's original figure to indicate that Point A is representative of a daily physically active human and point B is an occasionally active human. Based on a number of studies we propose that increases and decreases in daily physical activity over a time frame of hours to a few days places subjects between Points A and B. Thus, daily physical activity prevents the progression to Point B, making it impossible to continue from Point B, to Point C and Point D, overt diabetes. Therefore, only if continual physical inactivity is present can the progression to Point C, impaired glucose tolerance, and eventually into Point D, overt diabetes, occur. As Zimmet astutely and succinctly wrote, "A large proportion of cases of type 2 diabetes is preventable" ( 579).

18.5 T2D was preventable 35-70 years ago

Diabetes prevalence has risen from 1.4% in 1950 to 7.8% in the U.S. ( 367) and from 1% in 1975 to 9.7% in 2007-2008 in China ( 576). Zimmet commented, "In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioral factors such as a sedentary lifestyle, overly rich nutrition and obesity" ( 579). We will propose the notion that proper volumes of physical activity would essentially primarily prevent most of T2D, as illustrated by maintaining at point A in Fig. 12 .

18.6 Inactivity/exercise rapidly change insulin sensitivity

Reduced activity

LaMonte. Blair, and Church ( 300) hypothesized that the most proximal behavioral cause of insulin resistance is physical inactivity. Highly endurance trained men's high insulin sensitivity returns to sedentary levels after cessation of training for 38 hrs ( 391) or 60 hrs ( 72) as measured by euglycemic-hyperinsulimic clamp. Measured 12, 60, and 168 hrs after the last exercise bout, peripheral tissue glucose disposal dropped from 15.6 to 10.1 to 8.5 ml/kg/min, respectively, compared to 7.8 ml/kg/min in sedentary subjects ( 72). Similarly, 14, 38, 86, and 144 hr after the last exercise bout by endurance trained athletes glucose disposal declined from 9.40 to 7.78 to 6.82 to 7.11 mg/kg/min compared to 6.80 in sedentary subjects ( 391). Therefore, only days after ceasing exercise training, endurance athletes the same insulin sensitivity as long-term sedentary subjects. Like humans, rats who cease 3 weeks of voluntary wheel running drop their submaximal insulin-stimulated glucose uptake to sedentary values on the 2 nd day of no running in skeletal muscle normally recruited during wheel running ( 293). Less extreme reductions in physical activity, such as humans decreasing daily step numbers from 6203 to 1394 for 1 week lead to a 53% increase in the area under the curve for plasma insulin following an oral glucose tolerance test, a response that occurs due to reduced peripheral insulin sensitivity ( 389). Conversely, more extreme physical inactivity such as strict bed rest for 24-hr/day lasting 5 days ( 216), 7 days ( 46, 342, 495), and 9 days ( 7) is also associated with substantial increases in insulin resistance. Two days of bed rest did not affect insulin resistance ( 152).

Increasing activity improves insulin sensitivity in muscle

A single bout of muscle contraction increases insulin sensitivity in perfused hindquarters of healthy animals ( 242, 255, 434) and in the whole body of healthy humans ( 230, 343). Seven days of aerobic training increases whole body insulin sensitivity in 22- and 58-yr-old men and women ( 244), 66-yr-old men and women (BMI = 33) ( 486); 60- to 80-yr old men and women ( 112), and T2D patients ( 274, 444). Resistance training also enhances insulin sensitivity and improves glucose tolerance in a wide range of human subjects ( 526). A systemic review of 20 studies found that supervised resistance training improved glycemic control and insulin sensitivity in adults with T2D ( 206).

18.7 Biochemical mechanisms

Humans

In human subjects, a positive correlation exists between GLUT4 protein content in the vastus lateralis muscle with insulin sensitivity in both sexes ( 247). The relationship remained in men after adjustment for overall adiposity, regional adiposity, and CRF ( 247). Endurance-trained healthy individuals have higher GLUT4 mRNA and protein content than do sedentary ( 245, 467). Physical training also increases muscle GLUT4 protein and mRNA in patients with T2D ( 128). GLUT4 transcription is controlled in part by calcium signaling and the energy sensor 5′-AMP-activated protein kinase (AMPK) during exercise ( 435, 567, 568).

Skeletal muscle insulin sensitivity with contraction and inactivity

Conversely, much less effort has gone into investigating the mechanisms through which lack of physical activity decreases insulin sensitivity. Although low-grade inflammation can worsen insulin resistance in a variety of models circulating inflammatory markers were unchanged, while insulin resistance increased during 5 days of bed rest, implying that systemic inflammation is not a mechanism for initial insulin resistance ( 216). Reduced mitochondrial content or dysfunction has also been postulated to cause insulin resistance by leading to an increased accumulation of lipid intermediates in skeletal muscle ( 457). The lipid intermediates putatively activate serine kinases that reduce insulin signaling ultimately leading to reduced insulin stimulated GLUT4 translocation to the plasma membrane. However, the links between insulin resistance and an accumulation of lipid intermediates are associative at this time, and an increasing number of reports have found that the relationship does not always hold true ( 460). Another possibility is oxidative stress. Anderson et al. ( 13) report that both acute and chronic high-dietary fat intake lead to a dramatic increase in the H ₂O ₂-emitting potential of rat or human mitochondria in the absence of any change in respiratory function, consequently generating a shift to a more oxidized cellular redox environment that, if persistent, precedes the development of insulin resistance in skeletal muscle.

Insulin sensitivity in rat epitrochlearis muscle declines at a time (2 days after stopping 3 weeks of voluntary wheel running) when the mitochondrial marker, citrate synthase activity, remains unchanged and elevated from the wheel running ( 293). No differences in skeletal muscle mitochondria and insulin sensitivity existed between non-obese sedentary controls and hyperphagic, voluntary running in OLETF rats. Rector et al. ( 430) suggest a constant caloric overload and expanding adiposity may be the primary driver to insulin resistance in the OLETF sedentary animal model. Thyfault ( 511) suggested "It may be that a hypercaloric/lipidomic environment plus low energy flux (physical inactivity) is required to induce skeletal muscle insulin resistance in obesity" ( 511). Inactive skeletal muscles in physically inactive rats have insufficient electron transport flux to completely oxidize mitochondrial intermediates of ß-oxidation, producing lipid toxicity ( 281, 512). However, acute exercise prior to insulin stimulation can restore insulin stimulated glucose transport in muscle from obese Zucker rats ( 513), without improving signaling through the insulin-signaling pathway. Thus it appears that contraction induces a robust mitochondrial energy flux increasing in a coordinated fashion with both β-oxidation and the TCA cycle, that can override existing perturbations of the insulin-signaling pathway to enhanced insulin-stimulated glucose uptake in insulin resistant muscle in obese Zucker rats ( 512). The links between the contraction-induced energy flux and insulin action are at this time unknown, however according to a comprehensive review of the topic, the molecule Akt substrate 160 may play an integral role as it is activated by both insulin and muscle contraction and plays a major role in activation of GLUT4 translocation to the plasma membrane ( 82).

18.9 Clinical significance

Physical inactivity is a primary cause of loss of insulin sensitivity in skeletal muscle, and thus whole-body. Primary prevention of almost all of insulin resistance by high levels of daily physical activity is possible for almost all humans up their seventh decade of life ( 305). Continued long-term reductions in physical activity are a primary cause of insulin resistance.

The clinical consequences of insulin resistance, alone, have been delineated by Reaven ( 425): Some degree of glucose intolerance/impaired fasting glucose/impaired glucose tolerance, dylipidemia (↑ triglycerides, ↓ HDL-C, ↓ LDL partical size, ↑ postprandial accumulation of triglyceride-rich lipoproteins), endothelial dysfunction (↑ nonnuclear cell adhesion, ↑ plasma cellular adhesion molecules, ↑ plasma asymmetric dimethylarginine, ↓ endothelial-dependent vasodilation), Procoagulant factors (↑ plasminogen activator inhibitor-1, ↑ fibrinogen), hemodynamic factors (↑ sympathetic nervous system activity, ↑ renal sodium retention), markers of inflammation (↑ C-reactive protein, ↑ white blood cell count) abnormal uric acid metabolism (↑ plasma uric acid concentration, ↓ uric renal acid concentration), ↑ testosterone (ovary), and sleep-disordered breathing. By a direct cause of insulin resistance, physical inactivity indirectly, directly, or both in some cases (endothelial dysfunction) causes all of the aforementioned.

19. Prediabetes

Condition's definition A person with prediabetes has a fasting blood glucose level between 100 and 125 mg/dl and/or 2-hour blood glucose between 140 and 199 mg/dl during an oral glucose tolerance test.

19.2 Clinical significance

We speculate that physical inactivity is an actual cause of much of prediabetes cases in those <60 yrs of age. The speculation is based upon the Finnish DPS and DPP RCTs in prediabetics. However, to our knowledge, no large RCTs have been performed to test whether a physically active lifestyle over time primarily prevents prediabetes in healthy individuals as compared to healthy inactive individuals.

20. Type 2 diabetes (T2D)

20.1 Physical activity can reverse prediabetes

While early prediabetes, late prediabetes, and diabetes are in a continuum, they differ in success of primary prevention by physical activity. For instance, daily physical can reverse insulin resistance in healthy individuals (points B to A in the modified Bergman Fig. 12 ), and prediabetes (to point A). However, microvascular (retinopathy, neuropathy, nephropathy) damage in T2D seems to be non-repairable by physical activity ( 418)." Thus, the risk of chronic complications that are unable to be reversed by daily physical activity increases as a function of the duration of hyperglycemia, many of which maybe present in individuals when finally diagnosed with T2D ( 418).

20.3 Primary prevention of T2D - overview

The CDC Website states that progression to diabetes among those with prediabetes is not inevitable ( 88). The National Physical Activity Guidelines Advisory Committee Report (NPAGCR1) ( 412) states that usage of physical activity questionnaires in large prospective cohort and cross-sectional observational studies all show that increased physical activity levels show associations with reduced risk for developing T2D. A systemic review of follow-up, case-control or cross-sectional studies by Fogelholm ( 185) concludes for individuals with BMI of 25-35 having high BMI even with high physical activity were at a greater risk for the incidence of T2D and the prevalence of cardiovascular and diabetes risk factors, compared with normal BMI with low physical activity. Nonetheless, in men with a BMI of 25 or more, a history of hypertension, a positive parental history of diabetes, or any combination of these factors, the incidence of T2D declined by 41% from the lowest to the highest levels of energy expenditure ( 234) ( Table 10 ).

Table 10

Comments

Sample size

Country of study

Reference

↓ Adjusted relative risk of 15 and 57% between moderate and high compared to low physical activity

2017 men
2352 women

Finland

( 249)

↓ Adjusted relative risk of 13, 30 and 76% between low, moderate and high compared to no physical activity

4069 men
4034 women

Germany

( 338)

20.7 Physical activity can prevent T2D without weight loss

Primary prevention of T2D without weight loss has major public health importance due to media and medical emphasis on weight loss.

Randomized clinical trials (RCT)

Subjects were 80% less likely to develop T2D when they did not reach the percentage goal of weight loss, but achieved the goal with respect to exercise volume (more than four hours per week) as compared to the reference group, in the Finnish DPS ( 530).

20.9 T2D predisposing genes-environmental interactions

A complex disease such as T2D has, at present, 18 multiple candidate loci that account for only a small percentage (< 7%) of the total identifiable genetic load. Snyder at al. wrote,

"Thus, the interpretable genetic contributions that can be identified are quite minor... Presumably, either many low-frequency alleles at different loci contribute to the genetic load or perhaps the many phenotypes are because of other phenomena such as synergistic effects between variants at more than one locus or between different loci and factors in the environment, recurrent spontaneous mutations, or epigenetic defects." ( 484).

Contemporary hypotheses are that many individual rare gene variants play a much larger role in the genetic predisposition to T2D ( 436), but currently there is little data to support this speculation.

20.10 Clinical significance

Physical inactivity is an actual cause of insulin resistance and of prediabetes, and therefore, according to disease progression of T2D, itself. T2D is primarily prevented by primary prevention of insulin resistance (prevents movement from point A to B in the modified Bergman figure ( Fig. 12 ), and of decreased beta-cell insulin secretion and of prediabetes (prevents movement from point B to C in Bergman's Fig. 12 ).

T2D is estimated to cost men 11.6 life-years and 18.6 quality-adjusted life-years and women 14.3 life-years and 22.0 quality-adjusted life-years when at the age 40 years ( 366). Complications given at the American Diabetes Website ( 11) are: heart disease and stroke (death rate is 2-4 times greater than non-diabetics); hypertension (75% of diabetes); blindness (12,000-24,000 new cases/yr); kidney failure (~47,000 new cases/yr); neuropathy (60-70% of diabetics); and lower limb amputation (~71,000 cases/yr).

21. Non-alcoholic fatty liver disease (NAFLD)

21.2 Etiology

21.5 Cross-sectional

Habitual leisure-time physical activity, especially anaerobic, may play a protective role in NAFLD by a reduced rate of abdominal obesity in 24-70-yr old human subjects ( 578). Further, only the association with resistance physical activity remained significant with further adjustment for BMI. Lower VO ₂peak was associated with increasing NAFLD activity and with disease severity by NASH diagnosis ( 283).

21.6 Intervention

Maintaining or increasing physical activity provides health benefits for patients with fatty liver, independent of changes in weight ( 488). An intensive lifestyle intervention program can successfully produce a 7%-10% weight reduction and significant improvements in liver chemistry and histological activity in patients with NASH ( 420). Targeting weight loss by energy restriction alone or in combination with exercise training has been shown to reduce NAFLD pathology. In patients with and without NAFLD, nine months of diet and exercise intervention led to three important outcomes: 1) reduction in liver fat was approximately twice reduction of VAT; 2) subjects who resolved NAFLD tended to have higher CRF at prior to the intervention; and 3) VO ₂max at baseline was a predictor of change in liver fat, independently of total- and VAT mass ( 264). The study indicated that CRF fitness and liver fat are related to each other.

21.7 Clinical trials

Long-term RCTs examining the effects of exercise, independent of weight loss, on NAFLD are lacking.

21.8 Mechanisms

Two approaches were tested. The first approach compared OLETF rats with and without 16 weeks of voluntary running. OLETF rats that underwent the voluntary running had 3-fold higher rates of hepatic fatty acid oxidation (complete palmitate oxidization to CO ₂); lower TG synthesis [70% and 35% lower protein concentrations of fatty acid synthase and acetyl-coenzyme A carboxylase (ACC), respectively], and higher oxidative capacity (35% and 30% higher ACC phosphorylation and cytochrome c concentrations, respectively), as compared to sedentary OLETF rats ( 429). The second approach was to suddenly cease 16 wks of daily voluntary running by OLETF rats. The times for hepatic metabolic adaptations to occur with stoppage of running were: 2 days (malonyl-CoA protein increased while phospho-acetyl-CoA carboxylase (ACC) decreased) and 7 days (fatty acid synthase increased and cytochrome oxidase activity and fatty acid oxidation decreased). Thus, reduced physical activity for less than 7 days initiates biochemical sequences that leads to NAFLD in OLETF rats ( 428).

22. Cardiovascular diseases (CVD): All types

22.2 Known and unidentified risk factors

Of the identified CVD risk factors, modest percentage changes occur with habitual physical activity. Mora and Lee ( 349) indicate that changes in individual risk factors with physical activity are on the order of 5% for blood lipids, 3 to 5 mm Hg for blood pressure, and 1% for hemoglobin A1c, in contrast to the large (30% to 50%) reductions seen in CVD risk with physical activity.

22.3 Unknown pathophysiological mechanisms

Joyner and Green ( 261) proposed a global hypothesis that might include some, or all, the unknown ~40% and ~60% of unidentified risk factors by which physical activity reduces CVD and CHD, respectively. Their suggestions for additional risk factor candidates that are improved by habitual physical activity include:

Enhanced vagal tone via improved peripheral baroreflex function and central nervous system cardiovascular regulation. In populations, this will be protective and be seen as improved or maintained heart rate variability.

Enhanced or maintained endothelial function that will both favor vasodilatation and contribute to enhanced peripheral baroreflex function by limiting age- or risk factor-associated increases in vascular stiffness.

Positive interactions between enhanced endothelial function and sympathetic outflow that limit the effects of high levels of baseline sympathetic outflow on blood pressure ( 261).

22.4 Coronary vascular disease (CVD) gene-environmental interaction

CVD is a complex disease. Physical inactivity adaptations in gene expression are very complex, varying by tissue type and time. Thus CVD x physical inactivity interaction promises to be highly individualized, depending on the degree of accuracy of the desired prediction.

23. Presentation of individual cardiovascular diseases

The strategy for the presentation of individual cardiovascular diseases follows. The order of cardiovascular diseases presented will be coronary heart disease, peripheral artery disease, hypertension, stroke, and congestive heart failure. (Cross-references: Chronic cardiac disease)

24. Coronary heart disease (CHD)

24.1 Definition

CHD is a disease of the heart and the coronary arteries that is characterized by atherosclerotic arterial deposits that block blood flow to the heart, causing myocardial infarction.

24.5 Clinical significance

Physical inactivity is a cause of at least 1 of 3 deaths from CHD. Sufficient physical activity primarily prevents CHD.

25. Peripheral arterial disease (PAD)

25.1 Definition

Narrowed arteries reduce blood flow to limbs, sometimes causing leg pain, generally referred to as claudication when walking. (Cross-reference: Exercise and peripheral arterial insufficiency: Control of blood flow to cardiac and skeletal muscle during exercise)

25.3 Mechanisms

Mechanisms by which physical activity is primary prevention of PAD are potentially similar to those given for coronary artery disease.

26. Hypertension

26.1 Definition

With prehypertension, systolic blood pressure (SBP) is 120-139 mgHg and diastolic blood pressure (DBP) is 80-89 mmHg. Hypertension is defined as SBP ≥140 mmHg or DBP ≥90 mmHg, or taking antihypertensive medicine.

26.2 Etiology

In the United States, >62% of adults have blood pressures above optimal levels. The NPAGCR concluded that both aerobic and progressive resistance exercise cause reduced SBP and DBP in adult humans, although aerobic exercise evidence is stronger ( 412). The influence of exercise intensity on post-exercise hypotension occurred in dose-response fashion such that for each 10% increase in relative VO ₂peak, SBP decreased 1.5 mmHg and DBP 0.6 mmHg, thus showing a dose-response relationship for physical activity intensity and lowering of blood pressure post exercise (post-exercise hypotension) ( 156).

27. Stroke

27.1 Definition

Stroke is a sudden diminution or loss of consciousness, sensation, and voluntary motion caused by rupture or obstruction (as by a clot) of a blood vessel of the brain.

27.4 Clinical significance

Physical inactivity causes deteriorations in multiple mechanisms that cause stroke, as mentioned above. Physical activity could be primary prevention of 10-30% of stroke, depending on the volume of activity.

28. Congestive heart failure (CHF)

28.1 Definition

The heart fails to pump adequate amounts of blood through arteries to tissues, which causes blood to back up and accumulate in other parts of the body, such as lungs and feet. CHF is often accompanied by distension of the ventricles, peripheral and pulmonary (causing shortness of breath) edema.

28.2 Etiology

After 65 yrs of age, ~10 per 1000 individuals have CHF. Hypertension precedes 75% of CHF cases. RCTs for prevention of congestive heart failure are not available. Observational data supports the notion that habitual endurance training is primary prevention against development of CHF.

28.4 Clinical significance

Physical inactivity contributes development of CHF. Physical activity can primarily prevent some CHF.

29. Known mechanisms for CVD risk factors

29.1 Endothelial dysfunction

Conditions associated with endothelial dysfunction

Félétou and Vanhoutte's review states that endothelial dysfunction has been associated not only with hypertension or atherosclerosis, but also with the following long list of conditions:

Since then the term "endothelial dysfunction" has been referred to in the scientific literature more than 20,000 times (PubMed search, November 2005) and has been associated not only with hypertension or atherosclerosis, but also with physiological and pathophysiological processes, including aging, heart and renal failure, coronary syndrome, microalbuminuria, dialysis, thrombosis, intravascular coagulation, preeclampsia, Type I and Type II diabetes, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, postprandial lipemia, hypercholesterolemia, hyperhomocysteinemia, elevated asymmetric dimethylarginine plasma levels, inflammation, vasculitis, infections, sepsis, rheumatoid arthritis, periodontitis, trauma, transplantation, low birth weight, postmenopause in women, mental stress, sleep apnea syndrome, smoking, nitrate tolerance, glucocorticoids, and so on" ( 180).

The list of associations would now have to include physical inactivity since the 2005 list is out-of-date.

29.2 Atherogenic Dyslipidemia

29.3 Hemostasis

30. Deep vein thrombosis (DVT)

DVT is the formation of a blood clot ("thrombus") in a deep vein. its prevalence is ~12,000/yr with 6% dying within 1 month. DVT is caused by physical inactivity. The lack of shear stress along with low blood flow likely may account for deep vein thrombosis ("economy-class syndrome") at the back of vein valves where white cells adhere to fibrin strains ( 48). The clinical significance of DVT results when a clot breaks off as an embolus and flows to the lung where it blocks a portion of pulmonary blood flow, causing lack of gas exchange in pulmonary capillaries. Primary prevention is muscle pumping from muscle contraction that "squeezes" venous blood to return blood past venous valves back to the right atrium.

31. Cognitive Function

31.2 Epidemiology of developing better cognition

Research in exercise and prevention of cognitive decline is relatively new and moving rapidly. Recent reviews exist ( 239, 341).

Children

A 2003 meta-analysis in children (aged 4-18 yrs) demonstrated a significant positive relationship between physical activity levels and perceptual skills, intelligence quotient, achievement, verbal tests, mathematic tests, developmental level/academic readiness, with only an effect on memory not found ( 172). Chaddock et al. ( 91) found improvements in relational, but not item memory in children. Children who have low physical activity levels have poorer academic achievement scores and inferior cognitive performance as compared to physically fit children ( 70, 84, 91, 92, 100, 144, 172, 174, 237, 238, 273, 417, 565). A 2008 review concluded that exercise facilitates children's executive function, (i.e., organize thoughts and activities, prioritize tasks, manage time efficiently, and make decisions) similar to improvements reported for other age groups ( 520).

Older adults

18 RCTs (published prior to 2001) focused on aerobic physical activity interventions in older adults. Aerobic exercise had an overall effect size of 0.48 was found with the largest effect on executive functioning, followed by attention, visuospatial, and speed dependent processes ( 108). In a prospective study of 18,000 women aged 71-80 yrs old, higher levels of long-term regular physical activity were strongly associated with higher levels of cognitive function and a 20% lower risk of cognitive impairment ( 556). Physical inactivity (less than 3 bouts of exercise/week) increased the risk of dementia from 13.0 per 1000 person-years to 19.7 per 1000 person-years ( 306). Each 10 blocks that were walked/day in women >65 years old resulted in 13% less impairment in cognitive function ( 574). Moderate and high levels of physical activity were associated with significantly lower risks for Alzheimer disease and for dementia of any type ( 309). An inverse relationship between physical activity levels and dementia was found in men and women aged 65 years and older ( 413). Higher VO ₂peak was associated positively with preservation of cognitive function over a 6-year period in 349 subjects over the age of 55 ( 24).

31.3 Mechanisms

As a new frontier in inactivity disease, we chose to provide a more extensive presentation on the inactivity/exercise mechanisms for cognitive function.

Physiological/Structural

Biochemical adaptations

Genetic

31.4 Clinical Significance

Epidemiological, interventions, and mechanistic insights from human and rodent studies all suggest that physical inactivity can accelerate declines in cognitive function; a decline that be attenuated or potentially reversed by physical activity. However, questions remain regarding the best-practice for mode, duration, intensity, the long lasting effects, potential gender specific effects, and the interaction with genetic components.

32. Depression and anxiety

32.1 Definitions

32.2 Etiology

Depression is relatively common affecting 8% of women and 4% of men, having a lifetime prevalence of 16%, and an annual cost of $83 billion dollars in the United States ( 208). Anxiety is prevalent in 10% of the general public, has many similar symptoms and treatments to depression, but can also include a wide range of phobias. Both depression and anxiety are associated with increased risks of many other diseases. Genetic, biological, chemical, hormonal, environmental, psychological, and social factors all likely intersect to contribute to depression in women (see ( 369) or details). Some of these same factors play a role in men. For anxiety, disorders last at least 6 months and commonly occur along with other mental or physical illnesses, including alcohol or substance abuse.

32.3 Mechanisms

Biochemical adaptations

Genetic

32.4 Clinical significance

Physical inactivity causes up to 1/3 rd of depression. Physical activity can primarily prevent 20-30% of depression.

33. Bone (Osteoporosis)

33.1 Definition

Decrease in bone mass with decreased density and enlargement of bone spaces producing porosity and brittleness.

33.2 Etiology

Among males >50 yrs old, prevalence of osteoporosis and osteopenia was 6% and 47%, respectively; and in females >50 yrs of age, prevalence was 7% and 40%, respectively ( 202).

An actual cause: lack of exercise

Bone is lost from the lumbar spine and femoral neck at the rate of ~1% per year in sedentary pre-and postmenopausal women ( Fig. 13 ). Inactivity, i.e., reduced gravitational loading and muscle contraction forces on the skeleton, might contribute to aging-associated bone loss as suggested by the studies described below. (Exercise: the key to bone health through the life span)

33.3. Primary prevention

Finally, it is important to emphasize the site-specificity of exercise on bone. Only bones subject to loading will become stronger as adaptations are site-specific. Further, not all "weight-bearing" exercise is equivalent when it comes to increasing bone mass/strength, e.g., comparisons of walking (which does relatively little) < jogging < jumping.

33.4 Physiological mechanisms

Physical inactivity results in reduced mechanical, both gravitational and muscle contraction, forces which in turn induces catabolism (resorption) by promoting osteoclastogenesis with concurrent suppression of both bone formation and osteoblastogenesis. Dynamic exercise alters the balance between bone formation and resorption to favor anabolism through osteoblast recruitment and activity.

Mechanical loading of bone occurs in response to compressive forces from gravity during walking or running, or to in response to muscular forces at the bone attachments during contractions. Physical activity, alone, only increases strain on bone by ~0.1%. However, strains of 1-10% are needed to activate bone cells. The implication, then, is that a mechanism must therefore exist to amplify strains from physical activity (compressive impact forces from striking surfaces and tensile forces from contracting skeletal muscle at attachment sites to bone) to exceed the threshold needed to activate bone cells. Ozcivici et al. ( 394) conclude that mechanical targeting of the bone marrow stem-cell pool might, therefore, represent a novel, drug-free means of slowing the age-related decline of the musculoskeletal system.

33.6 Clinical consequences

Physical inactivity is a primary cause of bone loss in weight-bearing bones. Physical activity results in both gravitational and muscle-contraction loading of the skeleton and, therefore, is primary prevention of osteoporosis.

34. Osteoarthritis (OA)

34.1 Definition

Degeneration of cartilage and its underlying bone within a joint (Cross-reference: Osteoarthritis and exercise: cause and effects)

34 2 Etiology

The type and duration of physical activity is a key factor determining whether exercise is beneficial to joint health or not. Buckwalter wrote,

Participation in sports that cause minimal joint impact and torsional loading by people with normal joints and neuromuscular function may cause osteophyte (bony projections that form along joints) formation, but it has minimal, if any, effect on the risk of osteoarthritis. In contrast, participation in sports that subject joints to high levels of impact and torsional loading increases the risk of injury-induced joint degeneration. People with abnormal joint anatomy or alignment, previous joint injury or surgery, osteoarthritis, joint instability, articular surface incongruity or dysplasia, disturbances of joint or muscle innervation, or inadequate muscle strength have increased risk of joint damage during participation in athletics" ( 71).

34.3 Clinical significance

Primary prevention would be to avoid those sports predisposing to later life development of osteoarthritis.

35. Balance

Balance is defined as the ability to maintain the center of gravity for the body within the base of support that produces minimal postural sway. Its etiology can be related to lack of usage of nervous system controlling skeletal muscle movement against gravity. For example, living in space for as little as 9 days accelerates problems of equilibrium on standing, walking and coordination on return to Earth (caused by inappropriate neurovestibular responses) ( 540). With eyes closed on this platform astronauts complain of having no sensation of falling. Similar balance dysfunctions occur with aging. It is likely that improper balance upon return to Earth from spaceflight and with aging have a common denominator of insufficient exercise against gravity. Lack of appropriate balance occurs in later life. The NPAGCR ( 412) concluded that the strong evidence exists in old Americans that the risk of falls is reduced from physical activity programs that emphasize both balance training and muscle-strengthening activity with some aerobic activity, especially walking. The NPAGCR ( 412) further indicates that no evidence indicates that planned physical activity reduces falls in adults and older adults who are not at risk for falls. The clinical significance for primary prevention requires exercises that retain normal balance to reduce falls in individuals at risk for falls ( 124).

37. Rheumatoid Arthritis (RA)

RA is a chronic autoimmune disease characterized by inflammation of the joints, frequently accompanied by marked deformities, and ordinarily associated with manifestations of a general, or systemic, affliction. While no preventive measures are currently known, physical activity is critical to not allowing RA to progress. Studies show no harmful effects of physical activity, and some even show a positive effect in the reduction of symptoms ( 73). High-intensity physical activity is better than low at preventing the worsening of symptoms. The mechanism by which physical activity has a beneficial effect on RA might be its countering the global increase in inflammation that normally occurs during the progression of RA.

38. Cancer

38.1 Definition

A malignant tumor of potentially unlimited growth that expands locally by invasion and systemically by metastasis.

38.2 Comments on cancer types

Risks of only some cancers rise with physical inactivity

Physical inactivity increases the prevalence of some site-specific (colon, breast, and endometrial cancers), but, to date, not all cancer types. The specificity of cancer types enhanced by physical inactivity supports a notion that mechanisms of inactivity-induced cancers are specific to each site-specific cancer. Stated in an opposite manner, some cancer types are not caused by physical inactivity. (Cross-reference: Cancer)

Those cancers whose risk is enhanced by inactivity will be considered next.

39. Colon cancer

39.3 Mechanisms

39.4 Clinical significance

The lowest activity group has ~40% increased prevalence of colon cancer compared to the highest activity group. Physical activity is a primary preventer of colon cancer.

40. Breast cancer

40.1 Cross-sectional and longitudinal studies

The NPAGCR ( 412) concludes from 63 published studies that physical activity was associated with a medium reduction of 20% across all studies. However, the NPAGCR reports the range of reductions in breast cancer for all population-based case-control studies to be 20%-70% and for cohort studies to be 20%-80%.

The effect of physical activity on breast cancer reduction differs between pre- and post-menopausal conditions. A 2007 systemic review of 19 cohort and 29 case-control studies found a strong evidence for risk reductions ranging from 20% to 80% by physical activity for postmenopausal breast cancer ( 347). However, much weaker evidence is available for physical activities reduction on risk of premenopausal breast cancer, so no effect existed. Combining pre- and postmenopausal breast cancer resulted in a 15-20% decreased risk by physical activity. A trend analysis indicated a ~6% decrease in breast cancer risk for each additional hour of physical activity per week assuming that the level of activity would be sustained.

40.2 Mechanisms

Neilsen ( 373) suggests that physical inactivity might increase breast cancer prevalence by any or the following: higher than normal BMI, androgens, estrogens, lifetime exposure to estrogen, leptin, insulin, insulin resistance, TNF-α, IL-6, CRP, and inflammation. Lower levels of steroid hormone binding protein by physical inactivity have been suggested to increase breast cancer risk. The mechanisms by which long-term physical activity lowers postmenopausal breast cancer risk, however, remain unclear ( 373).

Thompson et al.'s comprehensive review provides extensive literature to support three hypotheses by which physical inactivity could enhance breast cancer's prevalence ( 509). Hypothesis 1 proposes that inactivity-induced changes in circulating growth factors and hormones activate the mTOR-signaling network to increase proliferation and decrease apoptosis in breast cells while stimulating new blood vessel formation. Hypothesis 2 states that inactivity increases breast cells responsiveness to physiological stresses, potentially through FoxO, Sirtuin, and/or adipokine/myokine signaling. Hypothesis 3 says that inactivity increases glucose and glutamine availability in mammary carcinomas, thereby attenuating breast cell apoptosis and, thus, increasing the accumulation of breast tumor masses.

40.3 Clinical significance

The lowest activity group has ~25% increased prevalence of breast cancer compared to the highest activity group. Physical activity is a primary preventer of breast cancer.

41. Endometrial cancer

The NPAGCR ( 412) found growing evidence to support reduced risk of endometrial cancers in physically active versus sedentary persons. A meta-analysis of prospective studies published through to December 2009 found that physical activity was clearly associated with a 30% lower risk of endometrial cancer ( 348).

42. Activity prevention of female reproductive disorders

42.2 Gestational diabetes mellitus (GDM)

Clinical significance

GDM occurs during pregnancy and having GDM increases the risk of T2D later in life in both mothers and their offspring carried during GMD. Physical inactivity would increase chances of GDM. Physical activity is primary prevention.

42.3 Preeclampsia

42.5 Polycystic ovarian syndrome (PCOS)

42.6 Female athlete triad (Triad)

Definition

A combination of disorders frequently found in female athletes that includes disordered eating, osteoporosis, and oligo- or amenorrhea.

The Triad is discussed in detail by an American College of Sports Medicine position stand ( 370). The position stand places emphasis on optimizing energy availability for primary prevention. The stand also states, "No pharmacological agent adequately restores bone loss or corrects metabolic abnormalities that impair health and performance in athletes with functional hypothalamic amenorrhea" ( 370). Eating disorders warrant psychotherapy.

42.7 Dysmenorrhea

43. Activity prevention of male reproductive disorders

43.1 Erectile Dysfunction (ED)

Interventional evidence

Utilizing a randomized-single bind design 110 obese men with ED, as defined by a International Index of Erectile Function (IIEF) less than 21, were either placed into an intervention group with the goal of 10% weight loss by walking 4 hours a week and reducing caloric intake or a control group. After 2 years, using an intent-to-treat analysis, the intervention group spent 195 min/wk doing physical activity and had a significant improvement in IIEF scores from 13.9 to 17, with no change in the control group. Furthermore, physical inactivity levels were independently associated with ED ( 170). In a follow up study using twice as many subjects this same group demonstrated that lifestyle intervention for two years reduced the prevalence of ED from 66% to 44% ( 169). Those within the lifestyle group that exercised more than 4 hours/wk were 1.9 times more likely to reverse ED than those in the lifestyle group that remained sedentary, correcting for changes in diet and other lifestyle habits. Using a higher intensity exercise of 75-80% VO ₂max for 60 minutes, 3 times a week, previously sedentary, but otherwise healthy men, had significant improvements in subjective sexual experiences. The improved sexual experiences correlated with the improvement in fitness ( 557).

Potential Mechanisms

Clinical significance of primary prevention Physical inactivity is one cause of ED. Physical activity can be a primary preventer of ED.

43.2 Prostate Cancer (PCa)

The overalle effects of physical activity on primary prevention of PCa are unclear. The NPAGCR concluded no association exists between physical activity and prostate cancer ( 412). On the other hand, the NPAGCR states a statistically significant trend towards decreasing prostate cancer risk was observed with increasing physical activity in several studies. Tertiary prevention may exist as Kenfield et al. ( 271) provided evidence that physical activity was associated with lower mortality and PCa mortality in men previously diagnosed with PCa. Barnard et al. ( 23) noted that serum from subjects performing regular aerobic exercise led to reduced growth and increased apoptosis of lymph node cancer of the prostate tumor cells in vitro.

44. Pain

44.1 Definition

A basic bodily sensation that is induced by a noxious stimulus, received by free nerve endings, and characterized by physical discomfort.

45. Digestive tract diseases

45.2 Diverticulitis

45.3 Gallbladder disease

46. Chronic respiratory diseases

46.1 Definition

Chronic diseases of the airways and other structures of the lung constitute chronic respiratory diseases. Some of the most common are asthma, chronic obstructive pulmonary disease (COPD), respiratory allergies, sleep apnea, occupational lung diseases and pulmonary hypertension. (Cross-reference: Chronic lung disease)

46.2 Etiology

Causes of these respiratory diseases are varied and include behavioral (smoking), environmental (air pollution and occupational hazards), and suppression of the immune system.

46.3 Physical inactivity

There are no studies to our knowledge showing that physical inactivity is associated with an increase in most chronic obstructive pulmonary diseases. With sleep apnea it is difficult to determine whether physical inactivity is a cause or a result of the sleep apnea resulting in a viscous cycle of less sleep coupled with less activity ( 549). With asthma, an interaction of an increased environmental pollution with physical activity may be the factor for more recent studies finding higher asthma in athletes. In two cross-sectional studies, asthma was more prevalent in swimmers [Odds ratio (OR) = 10], long distance runners (OR = 6), and power athletes (OR = 3-4), than in less active individuals ( 232, 233). However, in contrast, an older study of Finnish athletes that died between 1936 and 1985 showed that they were no more likely to have asthma and about 50% less likely to die of any pulmonary disease than non-athletes ( 291). Our suggestion is that increased environmental pollution interacting with physical inactivity, rather than physical activity per se, is a major cause for increased asthma rates in athletes. The conclusion is consistent with an increase in asthma in the general population as well in the last several decades.

The sum of data suggests that a "J-shaped" curve exists where physical inactivity and extreme physical activity increase the risk the greatest for acquiring upper respiratory tract infections (URTI). While some prospective studies suggest a greater risk for URTI after a competitive event ( 381, 382), with increasing amount of training ( 229, 408), and higher in faster finishers ( 487) others show no difference after an event ( 159) and lower UTRI with 6-7 METs/day of any activity ( 331). A decreased prevalence of UTI existed in two intervention studies utilizing lower levels of physical activity [one involving elderly women ( 380) and the other mildly obese females ( 383)] However, many of these studies contain methodological problems including, failure to report bouts of physical activity, UTRI are only reported never verified by virus analysis, higher medical awareness during high intensity training, contact with other infections (large marathon), stress, nutrition, supplements, and all the studies are focused on exercise not physical inactivity.

46.4 Mechanisms

There are several excellent reviews that the reader is directed to on immunosuppression following high levels of physical activity ( 64, 199, 401). The changes in immune function include low levels of lymphocytes and lymphocyte function ( 301), impaired phagocytosis, impaired neutrophilic function with prolonged exercise ( 401), neutrophil degranulation ( 400), reduced monocyte function ( 302), reduced oxidative burst activity, and potentially lower mucosal immunoglobulin levels ( 201).

46.5 Clinical significance

While regular moderate exercise reduces susceptibility to infection compared to sedentary, prolonged bouts of strenuous exercise cause a temporary depression of various aspects of immune function (e.g., neutrophil respiratory burst, lymphocyte proliferation, monocyte antigen presentation) for ~3-24 hr, e.g., after prolonged (>1.5 h), of moderate to high intensity (55-75% maximum O ₂ uptake) without food intake ( 199, 200). Periods of intensified training (overreaching) lasting 1 wk or more may result in longer lasting immune dysfunction ( 199, 200)

47. Chronic kidney disease (CKD)

CKDs damage the kidneys so that they are no longer capable of adequately removing fluids and wastes from the body or of maintaining the proper level of certain kidney-regulated chemicals in the bloodstream. (Cross-reference: Chronic renal failure). CKD is a secondary consequence of physical inactivity's increasing hypertension and T2D prevalence. Albumin to creatine ratio (ACR) is a marker of kidney function. The U.S. DPP found no change in ACR despite reductions in diabetes development with lifestyle reduction of T2D ( 136). In contrast, the Australian Diabetes, Obesity, and Lifestyle Study found that increased television watching or low self-reported leisure-time physical activity were associated with increased odds ratio of albuminuria and low estimated glomerular filtration rate in 6,000 subjects ( 325, 558). Physical inactivity was one of multiple covariants accounting for early decline in renal function in 1400 U.S. diabetic blacks ( 287). Norwegians (n = 65,000) undergoing no or little physical activity were twice as likely to have a low estimated glomerular filtration rate ( 215). In summary, physical inactivity contributes to development of CKD.

48. Clinical significance of physical inactivity as one cause of 35 chronic conditions

48.1 Volume of evidence

Much of the article has presented evidence to prove that physical inactivity is a primary, upstream event that causes substantial increases in risk factors for 30 chronic diseases/conditions ( Table 11 ; Fig. 3 ). The volume of evidence in itself is overwhelming. The clinical significance of physical activity itself is underappreciated as specific disease risk factors, themselves are often the prime objective of research and clinical care, rather than emphasis being placed on one major cause (physical inactivity) that is upstream of these risk factors.

Table 11

Disease/condition

Inactivity causes (Longer-term most days of the week implies years or decades while short-term is weeks to months)

Exercise primarily prevents\delays
* Just meet guidelines for moderate activity (30 min/day), not intent-treat.
** Our speculated asymptote for maximum in dose-response
~ Indicates our speculated percentage

VO 2max (CRF)

30-yr acceleration in loss

Yes, **Aerobic activity delays 30 yrs

48.2 Levels of evidence

Levels of evidence-based medicine vary in strength among the 30 chronic conditions caused by physical inactivity. Pressure toward evidence-based medicine has come from public and private health insurance providers, which refuse coverage of practices lacking in systematic evidence of usefulness. Levels of evidence are ranked for policy decision-making for health care distribution. The highest level of evidence is that there is a systemic review of RCT trials (Level 1) ( 94). The lowest level is based on mechanisms. However, models of extreme physical inactivity are so dramatic in the magnitude of health detriment that Human Institutional Research Boards IRB), for ethical reasons if side effects were to be muscle atrophy, for example, the IRB would consider the risk and then review what arrangements have been made to mitigate this risk. Our speculation is that IRBs would likely be hesitant, for ethical reasons, to approve RCTs lasting years if irreversible overt chronic disease were to occur because of physical inactivity. Therefore, RCTs to prove long-term physical inactivity causes a chronic disease are unlikely to occur.

In 2008 the DPP Research Group commented,

"Debate prevails about whether resources (human and financial) would be better spent on T2DM prevention or on its early detection and treatment. Early detection is feasible through use of the same simple tests used in prevention programs, and could be done much more economically than attempting to prevent diabetes at the population level. Allocation of resources to intensive management of patients with newly diagnosed diabetes could be preferable to prevention. A major drawback of this approach, however, is that many people will have already developed macrovascular disease (and, rarely, microvascular disease) before diagnosis. Nonetheless, no data from clinical trials that have specifically compared prevention with early detection and intensive treatment have yet been reported" ( 116).

49. Effectiveness of drug therapy for simultaneous primary prevention of 35 physical inactivity conditions

49.1 Inability to mimic adaptive health benefits of physical activity

The natural adaptations to exercise provide a higher therapeutic index (benefits/side effects) than any drug therapy could exceed ( Fig. 3 ). The high therapeutic index of exercise is in part due to its systemic complexity. It requires the integration of almost every physiological system (brain, neural, vascular, liver, adipose, muscle, etc.) to accomplish several basic physiological tasks such as movement and energy utilization. Since physical activity results in the whole body disruption of homeostasis in multiple organ systems, a drug therapy alone cannot replicate the entire ensemble its effects, without actually increasing physical activity. The complexity of physical activity is highlighted by comparison to other traits such as obesity. For instance, Reed et al. ( 431) estimate that 31% (extrapolated to 6000 genes) of all viable knockout mice have altered body weights. Such physiological complexity has been difficult to pharmacologically address with no FDA approved obesity drugs since 1999. Since the relative contribution of BMI for CVD and CHD has been estimated to be 10% and 7%, respectively ( 349), more than obesity is responsible for these diseases, making an "exercise pill" even less likely than obesity pill. We have published scientific criteria that must be met to legitimately use the terms `exercise pill' and `exercise mimetic' ( 53).

49.2 Clinical significance

Drugs will not substitute for all health benefits from physical activity in individuals medically capable of exercise.

50. Risk factors worsen over 6-12 months in RCTs

50.1 RCTs

The definition of chronic diseases contains the word "ongoing". Slentz, Houmard, and Kraus ( 481) cite evidence to support the notion, "continued sedentary lifestyle in overweight or obese individuals-particularly those who already have some metabolic abnormalities-comes at a high metabolic cost, as numerous health-related variables worsen over relatively short time periods" ( 51, 123, 218, 257). Examples from their own studies are given. Twelve markers that increase the risk of chronic diseases became worse in the 6-month inactive "control group", including increases in body weight, waist circumference, waist-to-hip ratio, VAT, total abdominal fat, fasting insulin, LDL particle number, small dense LDL and LDL-cholesterol; and decreases in insulin sensitivity, and fitness ( 35, 153, 246, 257, 284, 481).

Hunter et al. ( 251) have published similar decrements for inactive "control" groups. Aerobic- and resistance-exercise adherence for 1 yr prevented regain of VAT in healthy, overweight, premenopausal women following a weight loss of 12 kg ( 251). Specifically, aerobic or resistance exercise adherers did not change in visceral adipose tissue mass (1.6% and 0%, respectively) (80 min/wk), contrary to a 38% increased VAT in the non-exercise adherers. While aerobic and resistance exercise adherers still regained 3.1 and 3.9 kg of body weight, respectively, it was significantly less than the 6.2 kg regain in exercise non-adherers, which was similar to the 6.4 kg gained in the group that did not exercise ( 251). Thus, sedentary "controls" became less healthy by increasing risk factors for chronic diseases, compared to exercising groups in both the Slentz et al. ( 481) and the Hunter et al. ( 251) studies. Together the two studies illustrate contemporary inactive "control" groups have a progressive worsening for risk factors of chronic diseases that physical activity can be a primary prevention against. A similar theme was apparent for osteoporosis, presented earlier in this article, i.e., bones in non-bone loading group lose mass and density over a period of months. Importantly, the above studies fit the definition of "slow in its progress and of long continuance" for chronic diseases ( 551). The pathological events from sedentary lifestyle are slow in progress.

51. Primary prevention of physical inactivity: childhood developing adult disorders

51.2 Obesity in children and adolescents

Between the mid-1960's and mid-1980's, childhood and adolescent obesity ranged between 4%-6% ( Fig. 14 ). About 25 yrs later (mid-1980's to 2008), obesity (>95% BMI percentile for children in the 1960's) in children (6-11 yrs) had risen 5-fold from ~4% in 1963-1974 to 20% in 2007-2008, and in adolescents (12-19 yrs) rose 3-fold from ~5%-6% in between 1966-1980 to 18% in 2007-2008 ( Fig. 14 ) ( 386, 387). Even with a more liberal cutoff for overweight and obesity, 36% of children and 34% of adolescents, rather than 15% were above the 85 th percentile of the 1960's ( 386). Higher BMI during childhood is associated with an increased risk of CHD in adulthood ( 20).

51.5 Adult-onset diabetes in our adolescents

The estimated lifetime risk of developing diabetes for children born in 2000 is 32.8% for males and 38.5% for females, about 10-15% higher than current prevalence ( 366). This risk is higher for Hispanics, at 45.4% for males and 52.5% for females. In addition to developing complications, adolescents diagnosed as having diabetes have large reductions in life expectancy. For example, Narayan et al. ( 366) estimated that if diagnosed with T2D at age 20 yrs, males and females would die 17 and 18 years before normal, with a reduction of 27 and 30 quality-life adjusted years.

51.6 Metabolic syndrome in adolescents

A major problem with identifying the metabolic syndrome in children and adolescents is that there are no established criteria in this population ( 315). According to Cook et al., "In obese adolescents only, the prevalence rates were 44.2% using the definition of Cook/Ford ( 113), 26.2% using the adult criteria, 14.1% using the definition of Caprio, and 12.4% using the definition of Cruz" [As different modifications of adult criteria for the metabolic syndrome were applied, the specific criteria can be located in Table 1 of and Table 1 of ( 315)]. Children with BMI and waist circumference values greater than normal values are at increased risk for the adult metabolic syndrome ( 500). Morrison et al. ( 356) contend that evaluating 5- to 19-year-old children for metabolic syndrome and family history of diabetes could identify children at increased risk of adult metabolic syndrome and T2D, allowing prospective primary prevention of these outcomes.

51.9 Cognitive function

Children and adolescents who are physically inactive will develop less cognitive skills than more active cohorts, as discussed in Cognitive Function section.

51.10 Peak lifetime value determines years to reach clinical disease

Increases in bone mineral mass, skeletal muscle mass, and CRF occur throughout childhood and adolescence peaking and have their greatest lifetime values in the third decade of life. Thereafter with aging, their respective values progressively decline to lower values, at some age reaching a threshold past which an overt clinical condition has an increased probability of existing (osteoporosis, sarcopenia, and endurance frailty).

Bone: less weight-bearing activity by children/adolescents results in earlier osteoporosis

After the age of ~25 yrs, bone mineral density (BMD) is progressively lost. As some age, BMD passes a threshold of an overt clinical event (osteoporosis). For example, a 25-yr old individual with a BMD that is 90% of the mean peak BMD be osteoporotic ~30 yrs earlier than if they had a BMD 110% of the mean peak BMD ( Fig. 13 ).

The positive effect of mechanical loading on bone growth is greatest pre- and early-puberty in girls ( 25) and pre-puberty in boys ( 146). Thus, less load-bearing activity by children during skeletal growth is associated with smaller bone mass than in load-bearing children ( 438, 463). For example, girls starting at ages 9-15 had substantially greater increases in bone mineral content at lumbar spine and femoral neck if they had the highest physical activity levels during the 7-year follow-up as compared with those having the lowest physical activity levels ( 424). Thus, Rizzoli et al. ( 438) assert that childhood and adolescence is a key determinant of bone health and future fracture risk during adulthood.

Skeletal muscle: less weight-bearing activity by children/adolescents results in earlier sarcopenia

In an earlier section (Inactivity accelerates loss of functional capacities with chronological aging leading to premature death), Skeletal muscle power peaks about the third decade of life, and then declines thereafter ( Fig. 6 ). However, physically inactive individuals reached skeletal muscle frailty 24 yrs younger in age than masters' weight lifters.

CRF: less endurance-type play in children/adolescents increases risk of earlier death at old age

Fig. 4 in the earlier section (Inactivity accelerates loss of functional capacities with chronological aging leading to premature death), showed that VO ₂ max peaks at the third decade of life, and thereafter declines. However, physically inactive individuals passed below the threshold of aerobic frailty 30 yrs earlier in age than masters' aerobically trained individuals.

52. Public policy

52.1 Underappreciated cost

The NPAGCR ( 412) indicates that physical activity diminishes mortality by 30% in the U.S. Stated alternatively, physical inactivity increases mortality by 30%, or by 720,000 annual deaths (one death every 44 seconds). Our estimations are that U.S. health care costs of inactivity will range from $2.2-3.8 trillion in the first decade of the 21 st century, or $700 yearly ($7000 for the next decade) from each U.S. resident. Our estimate of physical inactivity's cost is in line with a) the Society of Actuaries estimate that overweight and obesity cost the U.S. $270 billion/year (cost includes increased need for medical care, and loss of economic productivity resulting from excess mortality and disability) ( 485) and b) the estimated nationwide cost of for physical inactivity and obesity of $507 billion with projected costs exceeding $708 billion in 2008 ( 98). We estimate that if every U.S. individual had 30 min of moderate physical activity/day obesity, annual U.S. health costs would be reduced ~4% ($100 billion out of $2.4 trillion), and additionally we speculate that if all U.S. individuals would approach the physical activity levels of U.S. Amish, obesity would be reduced ~8% ($200 billion out of $2.4 trillion). Further, physical activity reduces prevalence of many conditions that are not obesity co-morbidities, so we contend our estimates of physical inactivity are conservative and underestimates.

53. Conclusion

Physical activity, food, and reproduction are some of the minimal requirements for life. They evolved not as choices, but as requirements for individual and species survival. Modern humans have been able to engineer most physical activity out of daily life. Humans now have a choice not to be physically active. Conclusive and overwhelming scientific evidence, largely ignored and prioritized as low, exists for physical inactivity as a primary and actual cause of most chronic diseases. Thus, longer-term health was also engineered out with the successful removal of physical activity as a necessity for immediate survival. The comprehensive evidence herein clearly establishes that lack of physical activity affects almost every cell, organ, and system in the body causing sedentary dysfunction and accelerated death. The massive multifactorial nature of dysfunction caused by sedentarism means that just as food and reproduction remain as requirements for long-term continued human existence, physical activity is also a requirement to maximize health span and lifespan. The only valid scientific therapeutic approach to completely counter sedentary dysfunction is primary prevention with physical activity itself.

Acknowledgements

Jacob Brown, Marybeth Brown, Pam Hinton, Arthur Kramer, Thomas Meek, Scott Rector, Mike Roberts, Ron Terjung, John Thyfault, and Ryan Toedebusch for reviewing comments on specific sections of the article. Howard Wilson for constructing figures. Supported by anonymous gifts to FB. The article is dedicated to the continuing legacy of Charles M. Tipton and John O. Holloszy, who directly or indirectly touched the training of the authors.

Footnotes

¹ Major source for disease frequency data in chapter is US government report on physical activity by National Physical Activity Guidelines Advisory Committee, which will be referred to as NPAGCR.

References

8. Alibegovic AC, Sonne MP, Hojbjerre L, Bork-Jensen J, Jacobsen S, Nilsson E, Faerch K, Hiscock NJ, Mortensen B, Friedrichsen M, Stallknecht B, Dela F, Vaag A. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men. Am J Physiol Endocrinol Metab [[ PubMed] Google Scholar]

47. Blotner H. Effect of prolonged physical inactivity on tolerance of sugar. Arch Int Med. 1945;75:39-44. [ Google Scholar]

50. Booth FW, Laye MJ, Roberts MD. Lifetime sedentary living accelerates some aspects of secondary aging. J Appl Physiol. In Review. [[ PubMed] Google Scholar]

98. Chenoweth DLJ. The Economic Cost of Physical Inactivity and Excess Weight in American Adults. J Phys Act Health. 2008:148-163. [[ PubMed] Google Scholar]

173. Etnier JL. SW, Landers DM., Petruzello M., Han M. and Nowell P.,. The influence of physical fitness and exercise upon cognitive functioning: a meta-analysis. J Sport Exerc Psychol. 1997;19:249-277. [ Google Scholar]

210. Greenhaff PL, Hargreaves M. "Systems Biology" in Human Exercise Physiology: is it something different from Integrative Physiology? J Physiol. 2011 [[ PMC free article] [ PubMed] Google Scholar]

238. Hillman CH, Castelli DM, Buck SM. Aerobic fitness and neurocognitive function in healthy preadolescent children. Med Sci Sports Exerc. 2005;37:1967-1974. [ PubMed]

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Lack of exercise is a major cause of chronic diseases

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Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental ...

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This Ted talk estimates the current and future burden of cancer attributable to the most important cancer risk factors for Canadians, including air pollution, red meat consumption, smoking, UV radiation, sedentary behavior, obesity, and viruses.

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Priyanka Gogna: Cancer Prevention - No Quick Fix | TED Talk

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Almost 40% of cancer cases in Canada are due to modifiable environmental and lifestyle risk factors. What kinds of changes do we need to start making today to reduce our future cancer burden? Priyanka Gogna, a PhD candidate at Queen’s University discusses her work as part of the ComPARe Study-a nati…

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Explains why warm-ups need to consist of dynamic flexibility and not static stretching, and the importance of stretching for recovery.

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Stretching: Focus on flexibility

You can stretch anytime, anywhere. Just follow these tips to do it safely and effectively.
By Mayo Clinic Staff
You know exercise is important, but what about stretching? Does stretching take a back seat to your exercise routine? Not so fast.

Stretching may help you improve your range of motion and decrease your risk of injury, among other benefits.

Understand why stretching can help and how to stretch correctly.

Benefits of stretching

Studies about the benefits of stretching have had mixed results. Some research shows that stretching doesn't reduce muscle soreness after exercise. Other studies show that lengthening the muscle and holding the stretch immediately before a sprint may slightly worsen performance.

However, research has shown that stretching can help improve flexibility, and, as a result, the range of motion of your joints.

Better flexibility may:

Improve your performance in physical activities

Decrease your risk of injuries

Help your joints move through their full range of motion

Increase muscle blood flow

Enable your muscles to work most effectively

Improve your ability to do daily activities

You may learn to enjoy the ritual of stretching before or after hitting the trail, ballet floor or soccer field.

Stretching essentials

Before you plunge into stretching, make sure you do it safely and effectively. While you can stretch anytime, anywhere, proper technique is key. Stretching incorrectly can actually do more harm than good.

Use these tips to keep stretching safe:

Don't consider stretching a warmup. You may hurt yourself if you stretch cold muscles. Before stretching, warm up with light walking, jogging or biking at low intensity for 5 to 10 minutes. Even better, stretch after your workout when your muscles are warm.

Consider skipping stretching before an intense activity, such as sprinting or track and field activities. Some research suggests that pre-event stretching may actually decrease performance. Research has also shown that stretching immediately before an event weakens hamstring strength.

Strive for symmetry. Everyone's genetics for flexibility are a bit different. Rather than striving for the flexibility of a dancer or gymnast, focus on having equal flexibility side to side (especially if you have a history of a previous injury). Flexibility that is not equal on both sides may be a risk factor for injury.

Focus on major muscle groups. Concentrate your stretches on major muscle groups such as your calves, thighs, hips, lower back, neck and shoulders. Make sure that you stretch both sides.

Also stretch muscles and joints that you routinely use or that you use in your activity.

Don't bounce. Stretch in a smooth movement, without bouncing. Bouncing as you stretch can injure your muscle and actually contribute to muscle tightness.

Hold your stretch. Breathe normally and hold each stretch for about 30 seconds; in problem areas, you may need to hold for around 60 seconds.

Don't aim for pain. Expect to feel tension while you're stretching, not pain. If it hurts, you've pushed too far. Back off to the point where you don't feel any pain, then hold the stretch.

Make stretches sport specific. Some evidence suggests that it's helpful to do stretches involving the muscles used most in your sport or activity. If you play soccer, for instance, stretch your hamstrings as you're more vulnerable to hamstring strains.

Keep up with your stretching. Stretching can be time-consuming. But you can achieve the most benefits by stretching regularly, at least two to three times a week. Even 5 to 10 minutes of stretching at a time can be helpful.

Skipping regular stretching means that you risk losing the potential benefits. For instance, if stretching helped you increase your range of motion, your range of motion may decrease again if you stop stretching.

Bring movement into your stretching. Gentle movements, such as those in tai chi, Pilates or yoga, can help you be more flexible in specific movements. These types of exercises can also help reduce falls in older adults.

Also, try performing a "dynamic warmup." A dynamic warmup involves performing movements similar to those in your specific sport or physical activity at a low level. Then you speed up gradually and add intensity as you warm up.

Some people may also choose to add foam rolling before working out along with a dynamic warmup.

Know when to exercise caution

If you have a chronic condition or an injury, you might need to adjust your stretching techniques. For example, if you already have a strained muscle, stretching it may cause further harm. Talk to your doctor or physical therapist about the most appropriate way to stretch if you have any health concerns.

Also remember that stretching doesn't mean you can't get injured. Stretching, for instance, won't prevent an overuse injury.

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Show references

1. Franklin BA, et al. Exercise prescription and guidance for adults. https://www.uptodate.com/contents/search. Accessed Oct. 21, 2021.

2. AskMayoExpert. Physical activity (adult). Mayo Clinic; 2020.

3. Physical Activity Guidelines for Americans. 2nd ed. U.S. Department of Health and Human Services. https://health.gov/our-work/physical-activity/current-guidelines. Accessed Oct. 21, 2021.

4. More MC. Physical activity and exercise in older adults. https://www.uptodate.com/contents/search. Accessed Oct. 21, 2021.

5. Madden CC, et al. Netter's Sports Medicine. 2nd ed. Elsevier; 2018. https://www.clinicalkey.com. Accessed Nov. 1, 2021.

6. Riebe D, et al., eds. ACSM's Guidelines for Exercise Testing and Prescription. 10th ed. Wolters Kluwer Health Lippincott Williams & Wilkins; 2018.

7. Anderson BL, et al. The acute effects of foam rolling and dynamic stretching on athletic performance: A critically appraised topic. Journal of Sport Rehabilitation. 2021; doi:10.1123/jsr.2020-0059.

8. Polero P, et al. Physical activity recommendations during COVID-19: Narrative review. International Journal of Environmental Research and Public Health. 2020; doi:10.3390/ijerph18010065.

9. Berg, K. Stretching fundamentals. In: Prescriptive Stretching. 2nd ed. Kindle edition. Human Kinetics; 2020.

10. Gordon BT, et al., eds. Flexibility assessments and exercise programming for apparently healthy participants. In: ACSM's Resources for the Exercise Physiologist. 3rd ed. Kindle Edition. Wolters Kluwer; 2022.

11. Behm DG. Does stretching affect performance? In: The Science and Physiology of Flexibility and Stretching. Kindle edition. Routledge; 2019.

See more In-depth

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Overview of the crisis in the US and how we are failing our citizens when we have the means to reverse it.

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Poor nutrition is the No. 1 cause of illness in the United States and is responsible for more than half a million deaths per year, according to a white paper written by a panel of national nutrition experts.

" COVID-19 killed 100,000 Americans in just four months - a devastating tragedy of epic proportions. And, in just the last four months, poor diet has caused an estimated 107,000 U.S. deaths from cardiovascular diseases and diabetes, and 80,000 new cases of cancer. Half of U.S. adults have diabetes or prediabetes. It is also a devastating tragedy of epic proportions," says one of the coauthors, Dariush Mozaffarian, MD, DrPh, MPH, a cardiologist and the dean of the Friedman School of Nutrition Science and Policy at Tufts University in Boston. Dr. Mozaffarian is a member of the aforementioned panel, called the Federal Nutrition Research Advisory Group.

The strain that diet-related illnesses put on the U.S. healthcare system and government budgets has been further exposed and worsened by the COVID-19 pandemic, according to the paper, published on July 20 in the American Journal of Clinical Nutrition.

In the past 50 years, federal healthcare spending has grown from 5 to 28 percent of the federal budget, with 85 percent of that spending on the management of diet-related chronic diseases. The lack of good nutrition also poses a growing threat to America's military readiness as well as its ability to stay economically competitive in the world, according to the group; nearly three in four people between ages 17 and 24 do not qualify for military service, with obesity being the leading medical disqualifier.

Good Nutrition Is Essential for Overall Health

Close to 46 percent of adults and 56 percent of children in the United States have an overall poor-quality diet, according to the paper.

These figures are troubling because of the critical role nutrition plays in health, says Elizabeth Mayer-Davis, PhD, a distinguished professor of nutrition and medicine and chair of the department of nutrition at the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. "What you eat affects every system in the body throughout your entire life span," she says.

Dr. Mayer-Davis is a board member of the American Society for Nutrition, a group that voted to support this white paper, but she was not part of the group of experts who wrote it.

The field of nutrition has a very wide scope, which goes from basic science and molecular mechanisms and genetics all the way through policymaking and food recommendations, says Mayer-Davis.

"Overlaid on all that is what influences what we eat. That happens as a consequence of each person's culture, their family, their community, and what they like to eat, as well as what food they have access to and what they can afford," she says. "Once you put all those pieces together you have a really complicated mix."
RELATED: Black People Are at Greatest Risk of Losing Food Assistance When It's Tied to Work
The Majority of Americans Aren't at a Healthy Weight

Nearly three in four American adults and nearly one in five children are now either overweight or obese, as measured by their body mass index (BMI), wrote the authors, citing data collected by the Centers for Disease Control and Prevention (CDC). "The epidemic of overweight and obesity drives a lot of health outcomes and impacts your risk for heart disease, [type 2] diabetes, and several different types of cancer, as well as orthopedic conditions," says Mayer-Davis. Additional factors that increase the risk of developing a chronic disease include physical activity, alcohol use, smoking, and a family history of chronic disease, according to the CDC.

Overweight and obesity are the result of too many calories consumed compared with the level of physical activity that people have, she says. "Over a long period of time there's been an intake of not just too many calories in general, but of the types of food with a lot of added sugars and fats that are just adding calories without much nutritional value," says Mayer-Davis. These types of foods include soda and other sugar sweetened beverages, cakes, cookies, doughnuts, and dairy desserts like ice cream, according to the National Institutes of Health (NIH).
RELATED: Despite More Dieting, Americans Still Aren't Losing Weight
"We no longer live in a population that could be considered generally healthy with regard to weight; the majority of the population is overweight or obese and the minority of the population is of normal weight. That's a huge problem and a public health crisis," she says.

Nutrition Plays a Role in Health Disparities

Food insecurity impacts 1 in 8 Americans and is expected to more than double this year due to the economic effects of COVID-19.

The disparities in diet quality by race and ethnicity, education, and income continue to grow.

Poor diet can lead to lower achievement in school, lost productivity at work, more out-of-pocket healthcare expenses, and increased risk of chronic disease.

"Figuring out how to better address nutrition in this country is a critical part of addressing the really significant healthcare inequities we have in this nation," says Mayer-Davis.
RELATED: More Americans Exceed 200 Pounds, but Fewer See a Need to Lose Weight
The paper outlines several challenges in this effort:

"The role of diet in overweight and obesity and health equity turns out to be closely related. We need to improve the cost and availability of healthy food," says Mayer-Davis. "In many places, the available and inexpensive foods are those foods that have added sugars and fats, compounding the problem for communities where people are at higher risk for conditions like overweight and obesity and diabetes," she says.

Confusion Around Which Foods Are Healthy Can Lead to Poor Nutrition

Part of the problem is that many Americans are confused about what's healthy and what's not, according to the advisory council. There can be a few reasons for that, says Mayer-Davis. "Sometimes a study can get a lot of media attention and it's interpreted that a particular food or diet is the 'magic bullet.' This can cause people to focus too much on a certain issue and neglect other areas of their diet," she says.

In some cases, confusion can arise when studies on certain foods appear to give conflicting results, says Mayer-Davis. A good example of that is whether milk is good for you, she says. As far back as the 1980s, nutrition experts recommended skim or low-fat milk over full fat or whole milk to avoid too much saturated fat and weight gain, according to Harvard Medical School. On the other hand, a past meta-analysis of 16 observational studies published in the European Journal of Nutrition found that in many cases, consuming high-fat dairy (including milk) was actually associated with a lower risk of obesity.

We're also learning more about how people can have different responses to the same foods, which can also influence findings and make them appear inconsistent, says Mayer-Davis. "By the time this information can get to the pubic it can look like, 'Experts don't know if this food is good or bad,'" she says.

"People have to eat, and we have to make recommendations based on the best knowledge that we have, but it's incomplete knowledge. There's research that still needs to be done so that we can better understand these things," says Mayer-Davis.

Collaboration and Greater Investment in Nutrition Research Needed

"The paper calls for a restructuring of federal funding streams and expansion of the nutrition agenda as ways to enhance research funding, which may lead to answers in terms of policies, programs, and medical treatment," says Laura Caulfield, PhD, a professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Currently, funding at the National Institutes of Health (NIH) is separated among different disease states, with nutrition- and diet-related funding making up a small piece of each institute's budget, explains Dr. Caulfield.
RELATED: Why Are Healthy Eating Habits Important?
The authors propose improved coordination and communication within the NIH, along with greater investment in nutrition research that could lead to independent and synergistic benefits.

The advisory group also calls for the creation of federal offices and programs in nutrition to help accelerate needed discoveries and disseminate findings. "Collaboration and more communication between these groups would allow us to put knowledge into practice a lot faster. This could help address many of the nutrition-related problems that we have, including health inequity," says Mayer-Davis.

"The reality is that there's no one solution; all the different stakeholders need a way to work together, and this paper offers a few opportunities to help make that happen," she says.

Evidence Suggests Diet-Related Illnesses Have Worsened Outcomes in COVID-19

COVID-19 is a fast pandemic on top of a slow pandemic - one of diet-related poor metabolic health, including type 2 diabetes, obesity, and other conditions, Mozaffarian said in an interview published by TuftsNow.
RELATED: How Obesity May Increase the Risk of COVID-19 Complications
"These diet-related conditions greatly increase the risk of poor COVID-19 outcomes, including hospitalization and death. If we had a metabolically healthy population, all the evidence suggests COVID would have been much less severe, and we potentially would not have had to shut down the economy, shutter businesses and schools, and trigger many losses of jobs," said Mozaffarian.

Another important piece of this is that nutrition is crucial for a healthy immune system, says Mayer-Davis. "It's possible that whether or not someone gets ill at all with COVID-19 may be a function of their weight status. We don't know that yet, but we do know from research that nutrition is very important in immune function," she says.

Research has shown that people who are overweight or obese do not respond nearly as well to the flu vaccine, says Mayer-Davis. A study published in the Annals of the American Thoracic Society in November 2017 found that compared with vaccinated healthy-weight adults, vaccinated obese adults have twice the risk of influenza or influenza-like illness.

"What's happening right now with COVID-19 shows us yet another example of the importance of nutrition, and particularly the aspect of overweight and obesity in the population. It's really creating tremendous problems and contributing to health inequity," says Mayer-Davis.

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Poor Nutrition in the United States Poses Threats to Health, National Security, and Economy, Panel Says | Everyday Health

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Poor nutrition is the No. 1 cause of illness in the United States and is responsible for more than half a million deaths per year, according to a white paper written by a panel of national nutrition experts. " COVID-19 killed 100,000 Americans in just four months - a devastating tragedy of epic proportions.

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A visual on the different measures of body composition

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A lot of people look for fad diets, but they are often too extreme if you are struggling with obesity. This population needs tangible steps that are reasonable for them.

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National Institute of Diabetes and Digestive and Kidney Diseases

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Common treatments for overweight and obesity include losing weight through healthy eating, being more physically active, and making other changes to your usual habits. Weight-management programs may help some people lose weight or keep from regaining lost weight. Some people who have obesity are unable to lose enough weight to improve their health or are unable to keep from regaining weight. In such cases, a doctor may consider adding other treatments, including weight-loss medicines, weight-loss devices, or bariatric surgery.

Experts recommend losing 5 to 10 percent of your body weight within the first 6 months of treatment. [10] If you weigh 200 pounds, this means losing as little as 10 pounds. Losing 5 to 10 percent of your weight may

Healthy eating plan and regular physical activity

Following a healthy eating plan with fewer calories is often the first step in trying to treat overweight and obesity.

People who are overweight or have obesity should also start regular physical activity when they begin their healthy eating plan. Being active may help you use calories. Regular physical activity may help you stay at a healthy weight.

Learn more about healthy eating and physical activity to lose or maintain weight.

When combined with healthy eating, regular physical activity will help you lose weight and stay at a healthy weight.

Changing your habits

Changing your eating and physical activity habits and lifestyle is difficult, but with a plan, effort, regular support, and patience, you may be able to lose weight and improve your health. The following tips may help you think about ways to lose weight, engage in regular physical activity, and improve health over the long-term.

Be prepared for setbacks-they are normal. After a setback, like overeating at a family or workplace gathering, try to regroup and focus on getting back to your healthy eating plan as soon as you can. Try to eat only when you're sitting at your dining room or kitchen table. At work, avoid areas where treats may be available. Track your progress using online food or physical activity trackers, such as the Body Weight Planner, that can help you keep track of the foods you eat, your physical activity, and your weight. These tools may help you stick with it and stay motivated.

Set goals. Having specific goals can help you stay on track. Rather than "be more active," set a goal to walk 15 to 30 minutes before work or at lunch on Monday and Friday. If you miss a walk on Monday, pick it up again Tuesday.

Seek support. Ask for help or encouragement from your family, friends, or health care professionals. You can get support in person, through email or texting, or by talking on the phone. You can also join a support group. Specially trained health professionals can help you change your lifestyle.

Weight-management programs

Some people benefit from a formal weight-management program. In a weight-management program, trained weight-management specialists will design a broad plan just for you and help you carry out your plan. Plans include a lower-calorie diet, increased physical activity, and ways to help you change your habits and stick with them. You may work with the specialists on-site (that is, face-to-face) in individual or group sessions. The specialists may contact you regularly by telephone or internet to help support your plan. Devices such as smartphones, pedometers, and accelerometers may help you track how well you are sticking with your plan.

Some people may also benefit from online weight-management programs or commercial weight-loss programs.

Weight-loss medicines

When healthy eating and physical activity habits are not enough, your doctor may prescribe medicines to treat overweight and obesity.

You should try to stick with your healthy eating plan and continue getting regular physical activity while taking weight-loss medicines.

You may see ads for herbal remedies and dietary supplements that claim to help you lose weight. But many of these claims are not true. Some of these supplements can even have serious side effects. Talk with your doctor before taking any over-the-counter herbal remedies or dietary supplements for the purpose of trying to lose weight.

Weight-loss devices

Your doctor may consider weight-loss devices if you haven't been able to lose weight or keep from gaining back any weight you lost with other treatments. Because weight-loss devices have only recently been approved, researchers do not have long-term data on their safety and effectiveness. Weight-loss devices include

Electrical stimulation system. The electrical stimulation system uses a device a surgeon places in your abdomen with laparoscopic surgery. The device blocks nerve activity between your stomach and brain.

Gastric balloon system. For the gastric balloon system, a doctor places one or two balloons in your stomach through a tube that goes in your mouth. Once the balloons are in your stomach, the surgeon fills them with salt water so they take up more space in your stomach and help you feel fuller.

Gastric emptying system. A gastric emptying system uses a pump to drain part of the food from your stomach after a meal. The device includes a tube that goes from the inside of your stomach to the outside of your abdomen. About 20 to 30 minutes after eating, you use the pump to drain the food from your stomach through the tube into the toilet.

Bariatric surgery

Bariatric surgery includes several types of operations that help you lose weight by making changes to your digestive system. Bariatric surgery may be an option if you have extreme obesity and haven't been able to lose enough weight to improve your health or keep from gaining back the weight you lost with other treatments. Bariatric surgery also may be an option at lower levels of obesity if you have serious health problems, such as type 2 diabetes or sleep apnea, related to obesity. Bariatric surgery can improve many of the medical conditions linked to obesity, especially type 2 diabetes.

Special diets

Calorie-restricted diets

Your doctor may recommend a lower-calorie diet such as 1,200 to 1,500 calories a day for women and 1,500 to 1,800 calories a day for men. The calorie level depends on your body weight and physical activity level. A lower calorie diet with a variety of healthy foods will give you the nutrients you need to stay healthy.

Intermittent fasting

Intermittent fasting is another way of reducing food intake that is gaining attention as a strategy for weight loss and health benefits. Alternate-day fasting is one type of intermittent fasting that consists of a "fast day" (eating no calories to one-fourth of caloric needs) alternating with a "fed day," or a day of unrestricted eating. Researchers have conducted only a few studies of intermittent fasting as a strategy for weight loss. They have no long-term data on the safety and effectiveness of intermittent fasting for long-term weight maintenance.

References

[10] Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation. 2014;129:S102-S138.

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Treatment for Overweight & Obesity | NIDDK

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Common treatments for overweight and obesity include losing weight through healthy eating, being more physically active, and making other changes to your usual habits. Weight-management programs may help some people lose weight or keep from regaining lost weight. Some people who have obesity are unable to lose enough weight to improve their health or are unable to keep from regaining weight.

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Explains some basic physiological processes of cardiovascular endurance.

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Brain Bites - Cardiovascular Endurance with audio

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A breakdown on the difference between muscular strength and muscular endurance.

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Muscular strength and endurance are two important parts of your body's ability to move, lift things and do day-to-day activities. Muscular strength is the amount of force you can put out or the amount of weight you can lift. Muscular endurance is how many times you can move that weight without getting exhausted (very tired).

Benefits of Muscular Strength and Endurance

Muscular strength and endurance are important for many reasons:

Increase your ability to do activities like opening doors, lifting boxes or chopping wood without getting tired.

Reduce the risk of injury.

Help you keep a healthy body weight.

Lead to healthier, stronger muscles and bones.

Improve confidence and how you feel about yourself.

Give you a sense of accomplishment.

Allow you to add new and different activities to your exercise program.

Improving Muscular Strength and Endurance

There are many ways to improve muscular strength and endurance. A gym or fitness centre is a good place to go if you're interested in doing resistance training (also called strength training, weight training or weight lifting). This involves working a muscle or group of muscles against resistance to increase strength and power.

Resistance training can include using:

Equipment like medicine balls or weight machines

Resistance tubes or bands during exercises

Your own body as a weight, as you would do during push-ups or sit-ups

Of course, you don't have to go to a gym or buy exercise equipment to improve muscular strength and endurance. Doing normal daily activities like lifting groceries or walking up and down stairs can also help. You can also do many exercises at home that don't need equipment, such as push-ups and sit-ups. All you have to do is challenge your muscles to work harder or longer than they usually do.

Remember, if you're going to do strengthening exercises that involve lifting, it's important to use the correct techniques.

Last Reviewed: November, 2016
© 2016 Province of British Columbia. All rights reserved. May be reproduced in its entirety provided the source is acknowledged. This information is not meant to replace advice from your medical doctor or individual counselling with a health professional. It is intended for educational and informational purposes only.

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Muscular strength and endurance are two important parts of your body's ability to move, lift things and do day-to-day activities. Muscular strength is the amount of force you can put out or the amount of weight you can lift. Muscular endurance is how many times you can move that weight without getting exhausted (very tired).

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Mistakes to avoid when starting a fitness program

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Hitting the gym in search of a healthier body this year? Starting an exercise routine provides many benefits. Unfortunately, it isn't as simple as jumping on the treadmill and pushing start. Here are a few common mistakes made by new exercisers:

Not warming up. Your muscles need time to adjust to the new demands you will be putting on them with an exercise program. Start with a few minutes of light aerobic exercises before you go into your exercise routine.

Not cooling down. Don't just finish your workout and hit the shower. Take a few minutes to do some easy, slow exercises to lower your heart rate and stretch your muscles.

Not stretching enough. You should stretch before and after any exercise activity. Tight muscles can result in injury. As mentioned above, take a few minutes to warm up first.

Doing too much too soon. Making up for lost time in the gym during your very first workout is a recipe for disaster. Be realistic about your starting level, and progress slowly from there.

Lifting too much weight. This is a common mistake with men. Begin with a weight you can handle and gradually increase the amount as your muscles adapt. Stay mentally motivated when exercising.

Avoiding weights. This is a common mistake with women. Weight training is the best-kept secret to burning fat. Not only do you boost metabolism while you're working out, but you continue to elevate your body's metabolism up to 48 hours after you finished working out. Add at least 30-minutes of weight training to your program three times a week.

Not changing your diet. If one of your reasons for working out is weight loss, don't expect to drop any weight without changing your diet, too. To lose weight, maintain a daily caloric deficit with both exercise and nutrition (for example, cutting 250 calories a day from your diet and burning up an extra 250 exercising can help you drop one pound per week).

Talk to your doctor before starting any exercise program.

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Starting an Exercise Program? Avoid These 7 Mistakes. - Baptist...

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Hitting the gym in search of a healthier body this year? Starting an exercise routine provides many benefits. Unfortunately, it isn't as simple as jumping on the treadmill and pushing start. Here are a few common mistakes made by new exercisers: Not warming up. Your muscles need time to adjust...

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Over the last four decades, life expectancy in the United States has largely risen, although certain groups have experienced slight decreases in their life expectancy, gaining the attention of mortality experts and the media.