Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, including increasing growth and development, preventing aging, strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, and merely enjoyment. Frequent and regular physical exercise boosts the immune system and helps prevent "diseases of affluence" such as cardiovascular disease, type 2 diabetes, and obesity. It may also help prevent stress and depression, increase quality of sleep and act as a non-pharmaceutical sleep aid to treat diseases such as insomnia, help promote or maintain positive self-esteem, improve mental health, maintain steady digestion and treat constipation and gas, regulate fertility health, and augment an individual's sex appeal or body image, which has been found to be linked with higher levels of self-esteem. Childhood obesity is a growing global concern, and physical exercise may help decrease some of the effects of childhood and adult obesity. Some care providers call exercise the "miracle" or "wonder" drug—alluding to the wide variety of benefits that it can provide for many individuals.
In the United Kingdom two to four hours of light activity are recommended during working hours. This includes walking and standing. In the United States, the CDC/ACSM consensus statement and the Surgeon General's report states that every adult should participate in moderate exercise, such as walking, swimming, and household tasks, for a minimum of 30 minutes daily.
- 1 Classification
- 2 Health effects
- 3 Mechanism of effects
- 4 Public health measures
- 5 Exercise trends
- 6 Nutrition and recovery
- 7 History
- 8 Other animals
- 9 See also
- 10 Notes
- 11 References
- 12 Further reading
- 13 External links
Physical exercises are generally grouped into three types, depending on the overall effect they have on the human body:
- Aerobic exercise is any physical activity that uses large muscle groups and causes the body to use more oxygen than it would while resting. The goal of aerobic exercise is to increase cardiovascular endurance. Examples of aerobic exercise include cycling, swimming, brisk walking, skipping rope, rowing, hiking, playing tennis, continuous training, and long slow distance training.
- Anaerobic exercise, which includes strength and resistance training, can firm, strengthen, and tone muscles, as well as improve bone strength, balance, and coordination. Examples of strength moves are push-ups, pull-ups, lunges, and bicep curls using dumbbells. Anaerobic exercise also include weight training, functional training, eccentric training, Interval training, sprinting, and high-intensity interval training increase short-term muscle strength.
- Flexibility exercises stretch and lengthen muscles. Activities such as stretching help to improve joint flexibility and keep muscles limber. The goal is to improve the range of motion which can reduce the chance of injury.
Sometimes the terms 'dynamic' and 'static' are used. 'Dynamic' exercises such as steady running, tend to produce a lowering of the diastolic blood pressure during exercise, due to the improved blood flow. Conversely, static exercise (such as weight-lifting) can cause the systolic pressure to rise significantly (during the exercise).
A review of correlational studies suggest that physical exercise is important for maintaining physical fitness and can contribute positively to maintaining a healthy weight, regulating digestive health, building and maintaining healthy bone density, muscle strength, and joint mobility, promoting physiological well-being, reducing surgical risks, and strengthening the immune system. Some studies indicate that exercise may increase life expectancy and quality of life. Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential. People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.
According to the World Health Organization, lack of physical activity contributes to approximately 17% of heart disease and diabetes, 12% of falls in the elderly, and 10% of breast cancer and colon cancer.
Not everyone benefits equally from exercise. There is tremendous variation in individual response to training; where most people will see a moderate increase in endurance from aerobic exercise, some individuals will as much as double their oxygen uptake, while others can never augment endurance. However, muscle hypertrophy from resistance training is primarily determined by diet and testosterone. This genetic variation in improvement from training is one of the key physiological differences between elite athletes and the larger population. Studies have shown that exercising in middle age leads to better physical ability later in life.
The beneficial effect of exercise on the cardiovascular system is well documented. There is a direct correlation between physical inactivity and cardiovascular mortality, and physical inactivity is an independent risk factor for the development of coronary artery disease. Low levels of physical exercise increase the risk of cardiovascular diseases mortality.
Children who participate in physical exercise experience greater loss of body fat and increased cardiovascular fitness. Studies have shown that academic stress in youth increases the risk of cardiovascular disease in later years; however, these risks can be greatly decreased with regular physical exercise. There is a dose-response relation between the amount of exercise performed from approximately 700 to 2000 kcal of energy expenditure per week and all-cause mortality and cardiovascular disease mortality in middle-aged and elderly populations. The greatest potential for reduced mortality is in the sedentary who become moderately active. Studies have shown that since heart disease is the leading cause of death in women, regular exercise in aging women leads to healthier cardiovascular profiles. Most beneficial effects of physical activity on cardiovascular disease mortality can be attained through moderate-intensity activity (40% to 60% of maximal oxygen uptake, depending on age). Persons who modify their behavior after myocardial infarction to include regular exercise have improved rates of survival. Persons who remain sedentary have the highest risk for all-cause and cardiovascular disease mortality. According to the American Heart Association, exercise reduces blood pressure, LDL and total cholesterol, and body weight. It increases HDL cholesterol, insulin sensitivity, and exercise tolerance.
Although there have been hundreds of studies on exercise and the immune system, there is little direct evidence on its connection to illness. Epidemiological evidence suggests that moderate exercise has a beneficial effect on the human immune system; an effect which is modeled in a J curve. Moderate exercise has been associated with a 29% decreased incidence of upper respiratory tract infections (URTI), but studies of marathon runners found that their prolonged high-intensity exercise was associated with an increased risk of infection occurrence. However, another study did not find the effect. Immune cell functions are impaired following acute sessions of prolonged, high-intensity exercise, and some studies have found that athletes are at a higher risk for infections. Studies have shown that strenuous stress for long durations, such as training for a marathon, can suppress the immune system by decreasing the concentration of lymphocytes. The immune systems of athletes and nonathletes are generally similar. Athletes may have slightly elevated natural killer cell count and cytolytic action, but these are unlikely to be clinically significant.
Vitamin C supplementation has been associated with lower incidence of URTIs in marathon runners.
Biomarkers of inflammation such as C-reactive protein, which are associated with chronic diseases, are reduced in active individuals relative to sedentary individuals, and the positive effects of exercise may be due to its anti-inflammatory effects. In individuals with heart disease, exercise interventions lower blood levels of fibrinogen and C-reactive protein, an important cardiovascular risk marker. The depression in the immune system following acute bouts of exercise may be one of the mechanisms for this anti-inflammatory effect.
A systematic review evaluated 45 studies that examined the relationship between physical activity and cancer survivorship. According to the study results "There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer–specific, and colon cancer–specific mortality".
Physical exercise was correlated with a lower methylation frequency of two tumor suppressor genes, CACNA2D3 and L3MBTL. Hypermethylation of CACNA2D3 is associated with gastric cancer, while hypermethylation of L3MBTL is associated with breast cancer, brain tumors and hematological malignancies. A recent study indicates that exercise results in reduced DNA methylation at CpG sites on genes associated with breast cancer.
Physical exercise is becoming a widely accepted non-pharmacological intervention for the prevention and attenuation of cancer cachexia. "Cachexia is a multiorganic syndrome associated with cancer, characterized by inflammation, body weight loss (at least 5%) and muscle and adipose tissue wasting". Exercise triggers the activation of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), which suppresses FoxO- and NF-κB-dependent gene transcription during muscle atrophy that is induced by fasting or denervation; thus, PGC-1α may be a key intermediate responsible for the beneficial antiatrophic effects of physical exercise on cancer cachexia. The exercise-induced isoform PGC-1α4, which can repress myostatin and induce IGF1 and hypertrophy, is a potential drug target for treatment of cancer cachexia. Other factors, such as JUNB and SIRT1, that maintain skeletal muscle mass and promote hypertrophy are also induced with regular physical exercise.
The neurobiological effects of physical exercise are numerous and involve a wide range of interrelated effects on brain structure, brain function, and cognition. A large body of research in humans has demonstrated that consistent aerobic exercise (e.g., 30 minutes every day) induces persistent improvements in certain cognitive functions, healthy alterations in gene expression in the brain, and beneficial forms of neuroplasticity and behavioral plasticity; some of these long-term effects include: increased neuron growth, increased neurological activity (e.g., c-Fos and BDNF signaling), improved stress coping, enhanced cognitive control of behavior, improved declarative, spatial, and working memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory. The effects of exercise on cognition have important implications for improving academic performance in children and college students, improving adult productivity, preserving cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.
People who regularly perform aerobic exercise (e.g., running, jogging, brisk walking, swimming, and cycling) have greater scores on neuropsychological function and performance tests that measure certain cognitive functions, such as attentional control, inhibitory control, cognitive flexibility, working memory updating and capacity, and information processing speed. Aerobic exercise is also a potent antidepressant and euphoriant; as a result, consistent exercise produces general improvements in mood and self-esteem.
Regular aerobic exercise improves symptoms associated with a variety of central nervous system disorders and may be used as an adjunct therapy for these disorders. There is clear evidence of exercise treatment efficacy for major depressive disorder and attention deficit hyperactivity disorder. A large body of preclinical evidence and emerging clinical evidence supports the use of exercise therapy for treating and preventing the development of drug addictions. Reviews of clinical evidence also support the use of exercise as an adjunct therapy for certain neurodegenerative disorders, particularly Alzheimer’s disease and Parkinson's disease. Regular exercise is also associated with a lower risk of developing neurodegenerative disorders. Regular exercise has also been proposed as an adjunct therapy for brain cancers.
Physical exercise has established efficacy as an antidepressant in individuals with depression and current medical evidence supports the use of exercise as both a preventive measure against and an adjunct therapy with antidepressant medication for depressive disorders. A July 2016 meta-analysis concluded that physical exercise improves overall quality of life in individuals with depression relative to controls. One systematic review noted that yoga may be effective in alleviating symptoms of prenatal depression. The biomolecular basis for exercise-induced antidepressant effects is believed to be a result of increased neurotrophic factor signaling, particularly brain-derived neurotrophic factor.
Continuous aerobic exercise can induce a transient state of euphoria, colloquially known as a "runner's high" in distance running or a "rower's high" in crew, through the increased biosynthesis of at least three euphoriant neurochemicals: anandamide (an endocannabinoid), β-endorphin (an endogenous opioid), and phenethylamine (a trace amine and amphetamine analog).
A systematic review noted that, although limited, some evidence suggests that the duration of engagement in a sedentary lifestyle is positively correlated with a risk of developing an anxiety disorder or experiencing anxiety symptoms. It noted that additional research is needed in order to confirm these findings.
A 2010 review of published scientific research suggested that exercise generally improves sleep for most people, and helps sleep disorders such as insomnia. The optimum time to exercise may be 4 to 8 hours before bedtime, though exercise at any time of day is beneficial, with the possible exception of heavy exercise taken shortly before bedtime, which may disturb sleep. There is, in any case, insufficient evidence to draw detailed conclusions about the relationship between exercise and sleep.
According to a 2005 study, exercise is the most recommended alternative to sleeping pills for resolving insomnia. Sleeping pills are more costly than to make time for a daily routine of staying fit, and may have dangerous side effects in the long run. Exercise can be a healthy, safe and inexpensive way to achieve more and better sleep.
Too much exercise can be harmful. Without proper rest, the chance of stroke or other circulation problems increases, and muscle tissue may develop slowly. Extremely intense, long-term cardiovascular exercise, as can be seen in athletes who train for multiple marathons, has been associated with scarring of the heart and heart rhythm abnormalities. Specifically, high cardiac output has been shown to cause enlargement of the left and right ventricle volumes, increased ventricle wall thickness, and greater cardiac mass. These changes further result in myocardial cell damage in the lining of the heart, leading to scar tissue and thickened walls. During these processes, the protein troponin increases in the bloodstream, indicating cardiac muscle cell death and increased stress on the heart itself.
Inappropriate exercise can do more harm than good, with the definition of “inappropriate” varying according to the individual. For many activities, especially running and cycling, there are significant injuries that occur with poorly regimented exercise schedules. Injuries from accidents also remain a major concern, whereas the effects of increased exposure to air pollution seem only a minor concern.
In extreme instances, over-exercising induces serious performance loss. Unaccustomed overexertion of muscles leads to rhabdomyolysis (damage to muscle) most often seen in new army recruits. Another danger is overtraining, in which the intensity or volume of training exceeds the body's capacity to recover between bouts. One sign of Overtraining Syndrome (OTS) is suppressed immune function, with an increased incidence of upper respiratory tract infection (URTI). An increased incidence of URTIs is also associated with high volume/intensity training, as well as with excessive exercise (EE), such as in a marathon.
Stopping excessive exercise suddenly may create a change in mood. Exercise should be controlled by each body's inherent limitations. While one set of joints and muscles may have the tolerance to withstand multiple marathons, another body may be damaged by 20 minutes of light jogging. This must be determined for each individual.
Too much exercise may cause a woman to miss her periods, a symptom known as amenorrhea. This is a very serious condition which indicates a woman is pushing her body beyond its natural boundaries.
Mechanism of effects
Resistance training and subsequent consumption of a protein-rich meal promotes muscle hypertrophy and gains in muscle strength by stimulating myofibrillar muscle protein synthesis (MPS) and inhibiting muscle protein breakdown (MPB). The stimulation of muscle protein synthesis by resistance training occurs via phosphorylation of the mechanistic target of rapamycin (mTOR) and subsequent activation of mTORC1, which leads to protein biosynthesis in the ribosome via phosphorylation of mTORC1's immediate targets (the p70S6 kinase and the translation initiation factor 4EBP1). The suppression of muscle protein breakdown following food consumption occurs primarily via increases in plasma insulin; however, a suppression of MPB of comparable magnitude has also been shown to occur in humans from a sufficient elevation of plasma β-hydroxy β-methylbutyric acid.
Aerobic exercise induces mitochondrial biogenesis and an increased capacity for oxidative phosphorylation in the mitochondria of skeletal muscle, which is one mechanism by which aerobic exercise enhances submaximal endurance performance. These effects occur via an exercise-induced increase in the intracellular AMP:ATP ratio, thereby triggering the activation of AMP-activated protein kinase (AMPK) which subsequently phosphorylates peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis.
Other peripheral organs
Developing research has demonstrated that many of the benefits of exercise are mediated through the role of skeletal muscle as an endocrine organ. That is, contracting muscles release multiple substances known as myokines which promote the growth of new tissue, tissue repair, and multiple anti-inflammatory functions, which in turn reduce the risk of developing various inflammatory diseases. Exercise reduces levels of cortisol, which causes many health problems, both physical and mental. Endurance exercise before meals lowers blood glucose more than the same exercise after meals. There is evidence that vigorous exercise (90–95% of VO2 max) induces a greater degree of physiological cardiac hypertrophy than moderate exercise (40 to 70% of VO2 max), but it is unknown whether this has any effects on overall morbidity and/or mortality. Both aerobic and anaerobic exercise work to increase the mechanical efficiency of the heart by increasing cardiac volume (aerobic exercise), or myocardial thickness (strength training). Ventricular hypertrophy, the thickening of the ventricular walls, is generally beneficial and healthy if it occurs in response to exercise.
Central nervous system
The persistent long-term neurobiological effects of regular physical exercise[note 1] appear to be largely mediated by transient exercise-induced increases in the concentration of neurotrophic factors (e.g., BDNF, IGF-1, VEGF, and GDNF) and other biomolecules in peripheral blood plasma, which subsequently cross the blood–brain barrier and blood–cerebrospinal fluid barrier and bind to their associated receptors in the brain. Upon binding to their receptors in cerebral vasculature and brain cells (i.e., neurons and glial cells), these biomolecules trigger intracellular signaling cascades that lead to neuroplastic biological responses – such as neurogenesis, synaptogenesis, oligodendrogenesis, and angiogenesis, among others – which ultimately mediate the exercise-induced improvements in cognitive function.
Public health measures
Multiple component community-wide campaigns are frequently used in an attempt to increase a population's level of physical activity. A 2015 Cochrane review, however, did not find evidence supporting a benefit. The quality of the underlying evidence was also poor. Survery of brief interventions promoting physical activity found that they are cost-effective, although there are variations between studies.
Environmental approaches appear promising: signs that encourage the use of stairs, as well as community campaigns, may increase exercise levels. The city of Bogotá, Colombia, for example, blocks off 113 kilometers (70 mi) of roads on Sundays and holidays to make it easier for its citizens to get exercise. These pedestrian zones are part of an effort to combat chronic diseases, including obesity.
To identify which public health strategies are effective, a Cochrane overview of reviews is in preparation.
Physical exercise was said to decrease healthcare costs, increase the rate of job attendance, as well as increase the amount of effort women put into their jobs.
Children will mimic the behavior of their parents in relation to physical exercise. Parents can thus promote physical activity and limit the amount of time children spend in front of screens which may decrease the risk of childhood obesity.
Overweight children who participate in physical exercise experience greater loss of body fat and increased cardiovascular fitness. According to the Centers for Disease Control and Prevention in the United States, both children and adults should do 60 minutes or more of physical activity each day. Implementing physical exercise in the school system and ensuring an environment in which children can reduce barriers to maintain a healthy lifestyle is essential.
Worldwide there has been a large shift towards less physically demanding work. This has been accompanied by increasing use of mechanized transportation, a greater prevalence of labor saving technology in the home, and fewer active recreational pursuits. Personal lifestyle changes however can correct the lack of physical exercise.
Research in 2015 indicates integrating mindfulness to physical exercise interventions increases exercise adherence, self-efficacy and also has positive effects both psychologically and physiologically.
Nutrition and recovery
Proper nutrition is as important to health as exercise. When exercising, it becomes even more important to have a good diet to ensure that the body has the correct ratio of macronutrients while providing ample micronutrients, in order to aid the body with the recovery process following strenuous exercise.
Active recovery is recommended after participating in physical exercise because it removes lactate from the blood more quickly than inactive recovery. Removing lactate from circulation allows for an easy decline in body temperature, which can also benefit the immune system, as an individual may be vulnerable to minor illnesses if the body temperature drops too abruptly after physical exercise.
Several mass exercise movements were started in the early twentieth century to realise the benefits of exercise. The first and most significant of these in the UK was the Women's League of Health and Beauty founded in 1930 by Mary Bagot Stack that had 166,000 members in 1937.
However, the link between physical health and exercise (or lack of it) was only discovered in 1949 and reported in 1953 by a team led by Jerry Morris. Dr. Morris noted that men of similar social class and occupation (bus conductors versus bus drivers) had markedly different rates of heart attacks, depending on the level of exercise they got: bus drivers had a sedentary occupation and a higher incidence of heart disease, while bus conductors were forced to move continually and had a lower incidence of heart disease. This link had not previously been noted and was later confirmed by other researchers.
Physical exercise has been shown to benefit a wide range of other mammals, as well as salmon, juvenile crocodiles, and at least one species of bird.
However, several studies have shown that lizards display no benefit from exercise, leading them to be termed "metabolically inflexible". Indeed, damage from overtraining may occur following weeks of forced treadmill exercise in lizards.
Several studies of rodents have demonstrated that maternal  or juvenile access to wheels that allow voluntary exercise can increase the propensity to run as adults. These studies further suggest that physical activity may be more "programmable" (for discusison, see Thrifty phenotype) than food intake.
- Examples of these long-term effects include: marked improvements in executive function across all cognitive domains and small or moderate improvements in multiple forms of memory; increased gray matter volume in the hippocampus, prefrontal cortex, components of the basal ganglia, and other structures; and increased neural efficiency and greater functional connectivity between the left and right halves of the prefrontal cortex, the hippocampus and cingulate cortex.
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Research in children finds that higher fit and more active preadolescent children show greater hippocampal and basal ganglia volume, greater white matter integrity, elevated and more efficient patterns of brain activity, and superior cognitive performance and scholastic achievement. Higher fit and more physically active older adults show greater hippocampal, prefrontal cortex, and basal ganglia volume, greater functional brain connectivity, greater white matter integrity, more efficient brain activity, and superior executive and memory function. ...
Cognitive performance: Cross-sectional, observational, and randomized clinical trials of PA in late adulthood have demonstrated that engaging in PA may preserve and/or enhance cognitive function even in cognitively impaired individuals (e.g., ). Summaries of these studies can now be found in several meta-analyses, most of which confirm that PA positively influences cognitive function in late adulthood with small to moderate sized effects . In a meta-analysis of 18 randomized PA trials, engaging in moderate intensity PA resulted in enhanced cognitive function across all cognitive domains examined, but with the largest effect sizes for indices of executive function . Meta-analyses of longitudinal observational studies have also confirmed that self-reported engagement in PA is associated with nearly a 40% reduced risk of experiencing cognitive decline over several years . These, and other studies, make a convincing argument that both continuing to engage in, and starting to engage in, PA in late adulthood may have a profound effect on maintaining cognitive health, improving function, and reducing the risk of developing cognitive impairment.
Brain structure: There have been now more than 30 published studies of PA or fitness on brain structure in older adults (>60 years) with the majority showing positive associations (see ). Such effects are important since increasing age is associated with brain atrophy and loss of volume, which precedes and predicts conversion to dementia. Higher aerobic fitness levels have been associated with larger gray matter volumes in older adults in several areas including the frontal cortex [23,24], hippocampus [25,26], and caudate nucleus . Longitudinal observational studies have also shown that greater amounts of PA are associated with larger gray matter volumes in these regions, and greater volume is, in turn, associated with a reduced risk of cognitive impairment . These cross-sectional and observational results in older adults are further supported by clinical trials that have shown that six-months to one-year of regular PA is associated with an increase in both frontal cortex [29••,30] and hippocampal volume ... These effects on gray matter volume are accompanied by differences found in white matter integrity. For example, several studies have reported that higher cardiorespiratory fitness levels and PA are associated with greater white matter integrity along several tracts linking frontal and subcortical areas [34–36] and that greater changes in fitness after an intervention was associated with an increase in white matter integrity . In sum, there is now convincing evidence that PA and fitness influence brain structure, characterized by both gray matter volume and white matter integrity, in late adulthood.
- Paillard T, Rolland Y, de Souto Barreto P (July 2015). "Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review". J Clin Neurol 11 (3): 212–219. doi:10.3988/jcn.2015.11.3.212. PMC 4507374. PMID 26174783.
Aerobic physical exercise (PE) activates the release of neurotrophic factors and promotes angiogenesis, thereby facilitating neurogenesis and synaptogenesis, which in turn improve memory and cognitive functions. ... Exercise limits the alteration in dopaminergic neurons in the substantia nigra and contributes to optimal functioning of the basal ganglia involved in motor commands and control by adaptive mechanisms involving dopamine and glutamate neurotransmission.
- McKee AC, Daneshvar DH, Alvarez VE, Stein TD (January 2014). "The neuropathology of sport". Acta Neuropathol. 127 (1): 29–51. doi:10.1007/s00401-013-1230-6. PMC 4255282. PMID 24366527.
The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable ... Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration.
- Denham J, Marques FZ, O'Brien BJ, Charchar FJ (February 2014). "Exercise: putting action into our epigenome". Sports Med 44 (2): 189–209. doi:10.1007/s40279-013-0114-1. PMID 24163284.
Aerobic physical exercise produces numerous health benefits in the brain. Regular engagement in physical exercise enhances cognitive functioning, increases brain neurotrophic proteins, such as brain-derived neurotrophic factor (BDNF), and prevents cognitive diseases [76–78]. Recent findings highlight a role for aerobic exercise in modulating chromatin remodelers [21, 79–82]. ... These results were the first to demonstrate that acute and relatively short aerobic exercise modulates epigenetic modifications. The transient epigenetic modifications observed due to chronic running training have also been associated with improved learning and stress-coping strategies, epigenetic changes and increased c-Fos-positive neurons ... Nonetheless, these studies demonstrate the existence of epigenetic changes after acute and chronic exercise and show they are associated with improved cognitive function and elevated markers of neurotrophic factors and neuronal activity (BDNF and c-Fos). ... The aerobic exercise training-induced changes to miRNA profile in the brain seem to be intensity-dependent . These few studies provide a basis for further exploration into potential miRNAs involved in brain and neuronal development and recovery via aerobic exercise.
- Gomez-Pinilla F, Hillman C (January 2013). "The influence of exercise on cognitive abilities". Compr. Physiol. 3 (1): 403–428. doi:10.1002/cphy.c110063. PMC 3951958. PMID 23720292.
A second recent meta-analysis (162) corroborated Colcombe and Kramer’s (30) findings, in that aerobic exercise was related to attention, processing speed, memory, and cognitive control. ... Normal aging results in the loss of brain tissue (31), with markedly larger tissue loss evidenced in the frontal, temporal, and parietal cortices (16, 58, 149). As such, cognitive functions subserved by these brain regions (such as those involved in cognitive control and memory) are expected to decay more dramatically than other aspects of cognition. Specifically, age-related decreases in gray matter volume have been associated with decrements in a variety of cognitive control processes. ... Decreases in gray matter volume may result from several factors including loss in the number of neurons, neuronal shrinkage, reduction in dendritic arborization, and alterations in glia (158). Further, decreases in white matter (brain tissue composed primarily of myelinated nerve fibers) volume, which represent changes in connectivity between neurons, also occur as a result of aging. Loss of white matter volume further relates to performance decrements on a host of cognitive tasks ... aerobic fitness relates to larger hippocampal volume (23) and better relational memory performance (24), during preadolescent childhood. ... Specifically, those assigned to the aerobic training group demonstrated increases in gray matter in the frontal lobes, including the dorsal anterior cingulate cortex (ACC), supplementary motor area, middle frontal gyrus, dorsolateral region of the right inferior frontal gyrus, and the left superior temporal lobe (32). White matter volume changes were also evidenced for the aerobic fitness group with increases in white matter tracts within the anterior third of the corpus callosum (32). ... In addition, aerobic fitness has been shown to promote better functioning of brain, especially in neural networks involved in cognitive control of inhibition and attention (33). ... In addition to BDNF, the actions of IGF-1 and vascular endothelial growth factor (VEGF) (54) are considered essential for the angiogenic and neurogenic effects of exercise in the brain. ... Randomized and crossover clinical trials demonstrate the efficacy of aerobic or resistance training exercise (2–4 months) as a treatment for depression in both young and older individuals. ... exercise seems to have both preventative and therapeutic effects on the course of depression
- Erickson KI, Leckie RL, Weinstein AM (September 2014). "Physical activity, fitness, and gray matter volume". Neurobiol. Aging. 35 Suppl 2: S20–528. doi:10.1016/j.neurobiolaging.2014.03.034. PMC 4094356. PMID 24952993. Retrieved 9 December 2014.
We conclude that higher cardiorespiratory fitness levels are routinely associated with greater gray matter volume in the prefrontal cortex and hippocampus and less consistently in other regions. We also conclude that physical activity is associated with greater gray matter volume in the same regions that are associated with cardiorespiratory fitness including the prefrontal cortex and hippocampus. ... Meta-analyses (Colcombe and Kramer, 2003; Smith et al., 2010) suggest that the effects of exercise on the brain might not be uniform across all regions and that some brain areas, specifically those areas supporting executive functions, might be more influenced by participation in exercise than areas not as critically involved in executive functions. ... The effects appear to be general in the sense that many different cognitive domains are improved after several months of aerobic exercise, but specific in the sense that executive functions are improved more than other cognitive domains. ... physical activity and exercise may reduce the risk for AD (Barnes and Yaffe, 2011; Podewils et al., 2005; Sofi et al., 2011) ... Erickson et al. (2010) reported that greater amounts of physical activity were associated with greater gray matter volume 9-years later in the prefrontal cortex, anterior cingulate, parietal cortex, cerebellum, and hippocampus. ... higher fitness levels (VO2max) were associated with larger hippocampal volumes, better executive function, and faster processing speed. ... Verstynen et al. (2012) examined the association between cardiorespiratory fitness levels (VO2max) and the size of the basal ganglia ... Verstynen et al. (2012) found that higher fitness levels were associated with greater volume of the caudate nucleus and nucleus accumbens, and in turn, greater volumes were associated with better performance on a task-switching paradigm. ... That is, higher physical activity levels mitigated the detrimental effects of lifetime stress on the size of the hippocampus. ... The few randomized interventions published thus far have found results highly overlapping with the cross-sectional studies and suggest that the prefrontal cortex and hippocampus remain pliable in late life and that moderate intensity exercise for 6 months–1 year is sufficient for changing the size of these areas.
- Guiney H, Machado L (February 2013). "Benefits of regular aerobic exercise for executive functioning in healthy populations". Psychon Bull Rev 20 (1): 73–86. doi:10.3758/s13423-012-0345-4. PMID 23229442.
Executive functions are strategic in nature and depend on higher-order cognitive processes that underpin planning, sustained attention, selective attention, resistance to interference, volitional inhibition, working memory, and mental flexibility ... Data to date from studies of aging provide strong evidence of exercise-linked benefits related to task switching, selective attention, inhibition of prepotent responses, and working memory capacity; furthermore, cross-sectional fitness data suggest that working memory updating could potentially benefit as well. In young adults, working memory updating is the main executive function shown to benefit from regular exercise, but cross-sectional data further suggest that task-switching and post-error performance may also benefit. In children, working memory capacity has been shown to benefit, and cross-sectional data suggest potential benefits for selective attention and inhibitory control. ... Support for the idea that higher levels of aerobic activity may be associated with superior brain structure has been gained through cross-sectional studies in older adults and children (for a recent review, see Voss, Nagamatsu, et al., 2011). ... only those in the aerobic exercise group exhibited improved connectivity between the left and right prefrontal cortices, two areas that are crucial to the effective functioning of the fronto-executive network. ... Together, these studies provide evidence that regular aerobic exercise benefits control over responses during selective attention in older adults. ... aerobic fitness is a good predictor of performance on tasks that rely relatively heavily on inhibitory control over prepotent responses (e.g., Colcombe et al., 2004, Study 1; Prakash et al., 2011) and also that regular aerobic exercise improves performance on such tasks ... Overall, the results from the span and Sternberg tasks suggest that regular exercise can also confer benefits for the volume of information that children and older adults can hold in mind at one time.
- Erickson KI, Miller DL, Roecklein KA (2012). "The aging hippocampus: interactions between exercise, depression, and BDNF". Neuroscientist 18 (1): 82–97. doi:10.1177/1073858410397054. PMC 3575139. PMID 21531985.
Late adulthood is associated with increased hippocampal atrophy and dysfunction. ... However, there is strong evidence that decreased BDNF is associated with age-related hippocampal dysfunction, memory impairment, and increased risk for depression, whereas increasing BDNF by aerobic exercise appears to ameliorate hippocampal atrophy, improve memory function, and reduce depression. ... For example, longitudinal studies have reported between 1% and 2% annual hippocampal atrophy in adults older than 55 years without dementia ... Over a nine-year period, greater amounts of physical activity in the form of walking are associated with greater gray matter volume in several regions including prefrontal, temporal, and hippocampal areas. ... The prefrontal cortex and hippocampus deteriorate in late adulthood, preceding and leading to deficits in executive and memory function. We examined in this review the evidence that age-related changes in BDNF might at least partially explain hippocampal atrophy and increased risk for memory impairment. We can conclude that 1) decreases in BDNF protein expression are associated with poorer hippocampal function and increased rates of geriatric depression and AD. ... 3) Aerobic exercise enhances executive and memory function and reduces hippocampal atrophy in late adulthood, and this may be partially mediated through a BDNF pathway.
- Buckley J, Cohen JD, Kramer AF, McAuley E, Mullen SP (2014). "Cognitive control in the self-regulation of physical activity and sedentary behavior". Front Hum Neurosci 8: 747. doi:10.3389/fnhum.2014.00747. PMC 4179677. PMID 25324754.
Recent theory (e.g., Temporal Self-Regulation Theory; Hall and Fong, 2007, 2010, 2013) and evidence suggest that the relation between physical activity and cognitive control is reciprocal (Daly et al., 2013). Most research has focused on the beneficial effects of regular physical activity on executive functions-the set of neural processes that define cognitive control. Considerable evidence shows that regular physical activity is associated with enhanced cognitive functions, including attention, processing speed, task switching, inhibition of prepotent responses and declarative memory (for reviews see Colcombe and Kramer, 2003; Smith et al., 2010; Guiney and Machado, 2013; McAuley et al., 2013). Recent research demonstrates a dose-response relationship between fitness and spatial memory (Erickson et al., 2011) ... The effects of physical activity on cognitive control appear to be underpinned by a variety of brain processes including: increased hippocampal volume, increased gray matter density in the prefrontal cortex (PFC), upregulation of neurotrophins and greater microvascular density ... Together, this research suggests that an improvement in control processes, such as attention and inhibition or interference control, is associated with an improvement in self-regulation of physical activity. ... Hoang et al. (2013) found that young adults who initially exhibited low levels of physical activity and remained relatively inactive for 25 years had nearly twofold greater odds of impaired executive function compared with those who exhibited higher activity levels; very-low physical activity patterns were associated with even more pronounced declines in executive functioning. … sedentary behavior indirectly led to poor executive function through depressive symptoms (Vance et al., 2005). … sedentary individuals display less capacity to quickly and accurately switch between tasks.
- Schuch FB, Vancampfort D, Rosenbaum S, Richards J, Ward PB, Stubbs B (July 2016). "Exercise improves physical and psychological quality of life in people with depression: A meta-analysis including the evaluation of control group response". Psychiatry Res. 241: 47–54. doi:10.1016/j.psychres.2016.04.054. PMID 27155287.
Exercise has established efficacy as an antidepressant in people with depression. ... Exercise significantly improved physical and psychological domains and overall QoL. ... The lack of improvement among control groups reinforces the role of exercise as a treatment for depression with benefits to QoL.
- Pratali L, Mastorci F, Vitiello N, Sironi A, Gastaldelli A, Gemignani A (November 2014). "Motor Activity in Aging: An Integrated Approach for Better Quality of Life". Int. Sch. Res. Notices 2014: 257248. doi:10.1155/2014/257248. PMID 27351018.
Research investigating the effects of exercise on older adults has primarily focused on brain structural and functional changes with relation to cognitive improvement. In particular, several cross-sectional and intervention studies have shown a positive association between physical activity and cognition in older persons  and an inverse correlation with cognitive decline and dementia . Older adults enrolled in a 6-month aerobic fitness intervention increased brain volume in both gray matter (anterior cingulate cortex, supplementary motor area, posterior middle frontal gyrus, and left superior temporal lobe) and white matter (anterior third of corpus callosum) . In addition, Colcombe and colleagues showed that older adults with higher cardiovascular fitness levels are better at activating attentional resources, including decreased activation of the anterior cingulated cortex. One of the possible mechanisms by which physical activity may benefit cognition is that physical activity maintains brain plasticity, increases brain volume, stimulates neurogenesis and synaptogenesis, and increases neurotrophic factors in different areas of the brain, possibly providing reserve against later cognitive decline and dementia [89, 90].
- Cunha GS, Ribeiro JL, Oliveira AR (June 2008). "[Levels of beta-endorphin in response to exercise and overtraining]". Arq Bras Endocrinol Metabol (in Portuguese) 52 (4): 589–598. PMID 18604371.
Interestingly, some symptoms of OT are related to beta-endorphin (beta-end(1-31)) effects. Some of its effects, such as analgesia, increasing lactate tolerance, and exercise-induced euphoria, are important for training.
- Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR (2008). "The runner's high: opioidergic mechanisms in the human brain". Cereb. Cortex 18 (11): 2523–2531. doi:10.1093/cercor/bhn013. PMID 18296435.
The runner's high describes a euphoric state resulting from long-distance running.
- Josefsson T, Lindwall M, Archer T (2014). "Physical exercise intervention in depressive disorders: meta-analysis and systematic review". Scand J Med Sci Sports 24 (2): 259–272. doi:10.1111/sms.12050. PMID 23362828.
Physical activity has also become increasingly and firmly associated with improvements in mental health and psychological well-being (Mutrie, 2000; Landers & Arent, 2007). In particular, exercise is believed to be effective in preventing depression and also to significantly reduce depressive symptoms in clinical as well as in nonclinical populations (O’Neal et al., 2000; Landers & Arent, 2007). Several correlational studies show that exercise is negatively related to depressive symptoms (e.g., Galper et al., 2006; Hassmén et al., 2000). Moreover, a considerably large number of intervention studies have by now investigated the effect of various exercise programs on depression and the vast majority of them indicate that exercise significantly reduces depression (e.g., Blumenthal et al., 2007; Martinsen et al., 1985; Singh et al., 1997). ... To date, it is not possible to determine exactly how effective exercise is in reducing depression symptoms in clinical and nonclinical depressed populations, respectively. However, the results from the present meta-analysis as well as from seven earlier meta-analyses (North et al., 1990; Craft & Landers, 1998; Lawlor & Hopker, 2001; Stathopoulou et al., 2006; Mead et al., 2009; Rethorst et al., 2009; Krogh et al., 2011) indicate that exercise has a moderate to large antidepressant effect. Some meta-analytic results (e.g., Rethorst et al., 2009) suggest that exercise may be even more efficacious for clinically depressed people. ... In short, our final conclusion is that exercise may well be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program.
- Rosenbaum S, Tiedemann A, Sherrington C, Curtis J, Ward PB (2014). "Physical activity interventions for people with mental illness: a systematic review and meta-analysis". J Clin Psychiatry 75 (9): 964–974. doi:10.4088/JCP.13r08765. PMID 24813261.
This systematic review and meta-analysis found that physical activity reduced depressive symptoms among people with a psychiatric illness. The current meta-analysis differs from previous studies, as it included participants with depressive symptoms with a variety of psychiatric diagnoses (except dysthymia and eating disorders). ... This review provides strong evidence for the antidepressant effect of physical activity; however, the optimal exercise modality, volume, and intensity remain to be determined. ...
Few interventions exist whereby patients can hope to achieve improvements in both psychiatric symptoms and physical health simultaneously without significant risks of adverse effects. Physical activity offers substantial promise for improving outcomes for people living with mental illness, and the inclusion of physical activity and exercise programs within treatment facilities is warranted given the results of this review.
- Szuhany KL, Bugatti M, Otto MW (October 2014). "A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor". J Psychiatr Res 60C: 56–64. doi:10.1016/j.jpsychires.2014.10.003. PMC 4314337. PMID 25455510.
Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p < 0.001). Further, regular exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). ... Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans
- Lees C, Hopkins J (2013). "Effect of aerobic exercise on cognition, academic achievement, and psychosocial function in children: a systematic review of randomized control trials". Prev Chronic Dis 10: E174. doi:10.5888/pcd10.130010. PMC 3809922. PMID 24157077.
This omission is relevant, given the evidence that aerobic-based physical activity generates structural changes in the brain, such as neurogenesis, angiogenesis, increased hippocampal volume, and connectivity (12,13). In children, a positive relationship between aerobic fitness, hippocampal volume, and memory has been found (12,13). ... Mental health outcomes included reduced depression and increased self-esteem, although no change was found in anxiety levels (18). ... This systematic review of the literature found that [aerobic physical activity (APA)] is positively associated with cognition, academic achievement, behavior, and psychosocial functioning outcomes. Importantly, Shephard also showed that curriculum time reassigned to APA still results in a measurable, albeit small, improvement in academic performance (24). ... The actual aerobic-based activity does not appear to be a major factor; interventions used many different types of APA and found similar associations. In positive association studies, intensity of the aerobic activity was moderate to vigorous. The amount of time spent in APA varied significantly between studies; however, even as little as 45 minutes per week appeared to have a benefit.
- Mura G, Moro MF, Patten SB, Carta MG (2014). "Exercise as an add-on strategy for the treatment of major depressive disorder: a systematic review". CNS Spectr 19 (6): 496–508. doi:10.1017/S1092852913000953. PMID 24589012.
Considered overall, the studies included in the present review showed a strong effectiveness of exercise combined with antidepressants. ...
This is the first review to have focused on exercise as an add-on strategy in the treatment of MDD. Our findings corroborate some previous observations that were based on few studies and which were difficult to generalize.41,51,73,92,93 Given the results of the present article, it seems that exercise might be an effective strategy to enhance the antidepressant effect of medication treatments. Moreover, we hypothesize that the main role of exercise on treatment-resistant depression is in inducing neurogenesis by increasing BDNF expression, as was demonstrated by several recent studies.
- Ranjbar E, Memari AH, Hafizi S, Shayestehfar M, Mirfazeli FS, Eshghi MA (June 2015). "Depression and Exercise: A Clinical Review and Management Guideline". Asian J. Sports Med. 6 (2): e24055. doi:10.5812/asjsm.6(2)2015.24055. PMC 4592762. PMID 26448838.
Keeping in mind that exercise shows no medication side effects such as withdrawal symptoms (20), weight gain, dry mouth or insomnia (21), but shows potential health benefits such as weight reduction, it is highly recommended to use exercise as an adjunctive treatment for depression (22). New findings confirm that exercise can be recommended as a first-line treatment for mild to moderate depression; as an adjunct to medications (23); as an alternative to cognitive behavioral therapy (11); and in preventing depression in clinical as well as healthy populations (24-26). ... Although recent findings have shown that exercise can decrease depressive symptoms, there are still many questions and limitations to wider application of exercise in depression. For instance, there are deficiencies in methodological planning such as uncontrolled nonrandomized trials, small sample sizes, inadequate allocation concealment, lack of intention-to-treat analyses, non-blinded outcome assessments, and inclusion of subjects without clinical diagnosis that limit the interpretability of research outcomes (53).
Box 1: Patients with Depression Who May Particularly Benefit From Exercise Programs
Box 2: Depressive Disorders Other Than Major Depression That May Benefit From Exercise Programs
Box 3: The Characteristics of an Exercise Program that will Maximize the Anti-depressive Properties
- Den Heijer AE, Groen Y, Tucha L, Fuermaier AB, Koerts J, Lange KW, Thome J, Tucha O (July 2016). "Sweat it out? The effects of physical exercise on cognition and behavior in children and adults with ADHD: a systematic literature review". J. Neural. Transm. (Vienna). doi:10.1007/s00702-016-1593-7. PMID 27400928.
Cardio exercise seems acutely beneficial regarding various executive functions (e.g., impulsivity), response time and several physical measures. Beneficial chronic effects of cardio exercise were found on various functions as well, including executive functions, attention and behavior. The acute and chronic effects of non-cardio exercise remain more questionable but seem predominantly positive too. Research provides evidence that physical exercise represents a promising alternative or additional treatment option for patients with ADHD. Acute and chronic beneficial effects of especially cardio exercise were reported with regard to several cognitive, behavioral, and socio-emotional functions.
Cardio exercise: chronic effects
Cardio exercise (e.g., running and jumping) has also been linked to longer lasting effects on cognition in children with ADHD, resulting in improved attention (including auditory sustained attention and selective attention/information processing), executive functioning (including set shifting, (accuracy of) response inhibition and planning), verbal working memory, and cognitive speed (Chang et al. 2014; Choi et al. 2014; Gapin and Etnier 2010; Kang et al. 2011; Smith et al. 2013; Verret et al. 2012; Ziereis and Jansen 2015). However, a lack of robustness of chronic effects on cognition after cardio exercise is shown by some studies not reporting affected functions [e.g., (working) memory], and by studies not confirming significant beneficial long-term effects in the areas of inhibition, processing speed, planning, memory span, and continuous motor timing (Gapin and Etnier 2010; Smith et al. 2013). The lack of agreement in findings might partly be explained by the small sample sizes examined in the latter two studies (n = 14 and n = 18, respectively, which is less than the requested n = 34 for a one-factorial within subject design) and their consequential low statistical power. ...
It is assumed that physical exercise entails similar neurobiological effects as stimulants (e.g., increased availability of monoaminergic catecholamines in the brain, Fritz and O’Connor 2016; Wigal et al. 2013) and that these effects result in improved functioning in overlapping areas of cognition. A number of studies even showed (cognitive) gains of physical exercise on top of medication treatment (i.e., when children were on stimulant medication during the exercise bouts and tests; Choi et al. 2014; Gapin and Etnier 2010; Jensen and Kenny 2004; Kang et al. 2011; Maddigan et al. 2003; Mahon et al. 2008; McKune et al. 2003; Tantillo et al. 2002; Verret et al. 2012).
- Kamp CF, Sperlich B, Holmberg HC (July 2014). "Exercise reduces the symptoms of attention-deficit/hyperactivity disorder and improves social behaviour, motor skills, strength and neuropsychological parameters". Acta Paediatr. 103 (7): 709–14. doi:10.1111/apa.12628. PMID 24612421. Retrieved 14 March 2015.
The present review summarises the impact of exercise interventions (1–10 weeks in duration with at least two sessions each week) on parameters related to ADHD in 7-to 13-year-old children. We may conclude that all different types of exercise (here yoga, active games with and without the involvement of balls, walking and athletic training) attenuate the characteristic symptoms of ADHD and improve social behaviour, motor skills, strength and neuropsychological parameters without any undesirable side effects. Available reports do not reveal which type, intensity, duration and frequency of exercise is most effective in this respect and future research focusing on this question with randomised and controlled long-term interventions is warranted.
- Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (September 2013). "Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis". Neurosci Biobehav Rev 37 (8): 1622–1644. doi:10.1016/j.neubiorev.2013.06.011. PMC 3788047. PMID 23806439.
[exercise] efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. ... these data show that exercise can affect dopaminergic signaling at many different levels, which may underlie its ability to modify vulnerability during drug use initiation. Exercise also produces neuroadaptations that may influence an individual's vulnerability to initiate drug use. Consistent with this idea, chronic moderate levels of forced treadmill running blocks not only subsequent methamphetamine-induced conditioned place preference, but also stimulant-induced increases in dopamine release in the NAc (Chen et al., 2008) and striatum (Marques et al., 2008). ... [These] findings indicate the efficacy of exercise at reducing drug intake in drug-dependent individuals ... wheel running [reduces] methamphetamine self-administration under extended access conditions (Engelmann et al., 2013) ... These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuro-adaptive changes that develop during and following extended access to the drug. ... Exercise has been proposed as a treatment for drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes (see Table 4). ... Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes.
- Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology 61 (7): 1109–1122. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101.
Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008).
- Linke SE, Ussher M (2015). "Exercise-based treatments for substance use disorders: evidence, theory, and practicality". Am J Drug Alcohol Abuse 41 (1): 7–15. doi:10.3109/00952990.2014.976708. PMID 25397661.
The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been published. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.
- Zhou Y, Zhao M, Zhou C, Li R (July 2015). "Sex differences in drug addiction and response to exercise intervention: From human to animal studies". Front. Neuroendocrinol. doi:10.1016/j.yfrne.2015.07.001. PMID 26182835.
Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. ... As briefly reviewed above, a large number of human and rodent studies clearly show that there are sex differences in drug addiction and exercise. The sex differences are also found in the effectiveness of exercise on drug addiction prevention and treatment, as well as underlying neurobiological mechanisms. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation. ... In particular, more studies on the neurobiological mechanism of exercise and its roles in preventing and treating drug addiction are needed.
- Farina N, Rusted J, Tabet N (January 2014). "The effect of exercise interventions on cognitive outcome in Alzheimer's disease: a systematic review". Int Psychogeriatr 26 (1): 9–18. doi:10.1017/S1041610213001385. PMID 23962667.
Six RCTs were identified that exclusively considered the effect of exercise in AD patients. Exercise generally had a positive effect on rate of cognitive decline in AD. A meta-analysis found that exercise interventions have a positive effect on global cognitive function, 0.75 (95% CI = 0.32–1.17). ... The most prevalent subtype of dementia is Alzheimer’s disease (AD), accounting for up to 65.0% of all dementia cases ... Cognitive decline in AD is attributable at least in part to the buildup of amyloid and tau proteins, which promote neuronal dysfunction and death (Hardy and Selkoe, 2002; Karran et al., 2011). Evidence in transgenic mouse models of AD, in which the mice have artificially elevated amyloid load, suggests that exercise programs are able to improve cognitive function (Adlard et al., 2005; Nichol et al., 2007). Adlard and colleagues also determined that the improvement in cognitive performance occurred in conjunction with a reduced amyloid load. Research that includes direct indices of change in such biomarkers will help to determine the mechanisms by which exercise may act on cognition in AD.
- Rao AK, Chou A, Bursley B, Smulofsky J, Jezequel J (January 2014). "Systematic review of the effects of exercise on activities of daily living in people with Alzheimer's disease". Am J Occup Ther 68 (1): 50–56. doi:10.5014/ajot.2014.009035. PMID 24367955.
Alzheimer’s disease (AD) is a progressive neurological disorder characterized by loss in cognitive function, abnormal behavior, and decreased ability to perform basic activities of daily living [(ADLs)] ... All studies included people with AD who completed an exercise program consisting of aerobic, strength, or balance training or any combination of the three. The length of the exercise programs varied from 12 weeks to 12 months. ... Six studies involving 446 participants tested the effect of exercise on ADL performance ... exercise had a large and significant effect on ADL performance (z = 4.07, p < .0001; average effect size = 0.80). ... These positive effects were apparent with programs ranging in length from 12 wk (Santana-Sosa et al., 2008; Teri et al., 2003) and intermediate length of 16 wk (Roach et al., 2011; Vreugdenhil et al., 2012) to 6 mo (Venturelli et al., 2011) and 12 mo (Rolland et al., 2007). Furthermore, the positive effects of a 3-mo intervention lasted 24 mo (Teri et al., 2003). ... No adverse effects of exercise on ADL performance were noted. ... The study with the largest effect size implemented a walking and aerobic program of only 30 min four times a week (Venturelli et al., 2011).
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- Blondell SJ, Hammersley-Mather R, Veerman JL (May 2014). "Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies". BMC Public Health 14: 510. doi:10.1186/1471-2458-14-510. PMC 4064273. PMID 24885250.
Longitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia. A case can be made for a causal interpretation. Future research should use objective measures of physical activity, adjust for the full range of confounders and have adequate follow-up length. Ideally, randomised controlled trials will be conducted. ... On the whole the results do, however, lend support to the notion of a causal relationship between physical activity, cognitive decline and dementia, according to the established criteria for causal inference.
- Cormie P, Nowak AK, Chambers SK, Galvão DA, Newton RU (April 2015). "The potential role of exercise in neuro-oncology". Front. Oncol. 5: 85. doi:10.3389/fonc.2015.00085. PMC 4389372. PMID 25905043.
- Gong H, Ni C, Shen X, Wu T, Jiang C (February 2015). "Yoga for prenatal depression: a systematic review and meta-analysis". BMC Psychiatry 15: 14. doi:10.1186/s12888-015-0393-1. PMC 4323231. PMID 25652267.
- Tantimonaco M, Ceci R, Sabatini S, Catani MV, Rossi A, Gasperi V, Maccarrone M (2014). "Physical activity and the endocannabinoid system: an overview". Cell. Mol. Life Sci. 71 (14): 2681–2698. doi:10.1007/s00018-014-1575-6. PMID 24526057.
The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system (ECS), composed of endogenous lipids, their target receptors, and metabolic enzymes. Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body. ... the evidence that PA induces some of the psychotropic effects elicited by the Cannabis sativa active ingredient Δ9-tetrahydrocannabinol (Δ9-THC, Fig. 1), like bliss, euphoria, and peacefulness, strengthened the hypothesis that endocannabinoids (eCBs) might mediate, at least in part, the central and peripheral effects of exercise . ... To our knowledge, the first experimental study aimed at investigating the influence of PA on ECS in humans was carried out in 2003 by Sparling and coworkers , who showed increased plasma AEA content after 45 min of moderate intensity exercise on a treadmill or cycle ergometer. Since then, other human studies have shown increased blood concentrations of AEA ... A dependence of the increase of AEA concentration on exercise intensity has also been documented. Plasma levels of AEA significantly increased upon 30 min of moderate exercise (heart rate of 72 and 83 %), but not at lower and significantly higher exercise intensities, where the age-adjusted maximal heart rate was 44 and 92 %, respectively ... Several experimental data support the hypothesis that ECS might, at least in part, explain PA effects on brain functions, because: (1) CB1 is the most abundant GPCR in the brain participating in neuronal plasticity ; (2) eCBs are involved in several brain responses that greatly overlap with the positive effects of exercise; (3) eCBs are able to cross the blood–brain barrier ; and (4) exercise increases eCB plasma levels [64–67].
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According to the 'endorphins hypothesis', exercise augments the secretion of endogenous opioid peptides in the brain, reducing pain and causing general euphoria. ... Based upon a large effect size, the results confirmed the endorphins hypothesis demonstrating that exercise leads to an increased secretion of endorphins which, in turn, improved mood states.
β-Endorphin, an endogenous μ-opioid receptor selective ligand, has received much attention in the literature linking endorphins and depression or mood states. ... exercise of sufficient intensity and duration can increase circulating β-endorphin levels. ... Moreover, a recent study demonstrated that exercise and physical activity increased β-endorphin levels in plasma with positive effects on mood. Interestingly, the researchers reported that, independently of sex and age, dynamic anaerobic exercises increased β-endorphin, while resistance and aerobic exercises seem to only have small effects on β-endorphins. ... The results showed that mood tends to be higher in a day an individual exercises as well as that daily activity and exercise overall are strongly linked with mood states. In line with these findings, a recent study showed that exercise significantly improved mood states in non-exercises, recreational exercisers, as well as marathon runners. More importantly, the effects of exercise on mood were twofold in recreational exercisers and marathon runners.
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The 24 hour mean urinary concentration of phenylacetic acid was increased by 77% after exercise. ... These results show substantial increases in urinary phenylacetic acid levels 24 hours after moderate to high intensity aerobic exercise. As phenylacetic acid reflects phenylethylamine levels3 , and the latter has antidepressant effects, the antidepressant effects of exercise appear to be linked to increased phenylethylamine concentrations. Furthermore, considering the structural and pharmacological analogy between amphetamines and phenylethylamine, it is conceivable that phenylethylamine plays a role in the commonly reported "runners high" thought to be linked to cerebral β-endorphin activity. The substantial increase in phenylacetic acid excretion in this study implies that phenylethylamine levels are affected by exercise. ... A 30 minute bout of moderate to high intensity aerobic exercise increases phenylacetic acid levels in healthy regularly exercising men. The findings may be linked to the antidepressant effects of exercise.
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The pharmacology of TAs might also contribute to a molecular understanding of the well-recognized antidepressant effect of physical exercise . In addition to the various beneficial effects for brain function mainly attributed to an upregulation of peptide growth factors [52,53], exercise induces a rapidly enhanced excretion of the main β-PEA metabolite β-phenylacetic acid (b-PAA) by on average 77%, compared with resting control subjects , which mirrors increased β-PEA synthesis in view of its limited endogenous pool half-life of ~30 s [18,55].
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It has also been suggested that the antidepressant effects of exercise are due to an exercise-induced elevation of PE .
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Nonetheless, as the overall MPS response was similar, this cellular signalling distinction did not translate into statistically distinguishable anabolic effects in our primary outcome measure of MPS. ... Interestingly, although orally supplied HMB produced no increase in plasma insulin, it caused a depression in MPB (−57%). Normally, postprandial decreases in MPB (of ∼50%) are attributed to the nitrogen-sparing effects of insulin since clamping insulin at post-absorptive concentrations (5 μU ml−1) while continuously infusing AAs (18 g h−1) did not suppress MPB (Greenhaff et al. 2008), which is why we chose not to measure MPB in the Leu group, due to an anticipated hyperinsulinaemia (Fig. 3C). Thus, HMB reduces MPB in a fashion similar to, but independent of, insulin. These findings are in-line with reports of the anti-catabolic effects of HMB suppressing MPB in pre-clinical models, via attenuating proteasomal-mediated proteolysis in response to LPS (Eley et al. 2008).
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Exercise training stimulates mitochondrial biogenesis, yet an emerging hypothesis is that training also induces qualitative regulatory changes. ... The training-induced upregulation in mitochondrial volume and Vmax of respiration is well documented by morphological studies and functional observations at the level of single mitochondrial enzymes and whole mitochondria. In healthy humans, Vmax of mitochondrial oxidative phosphorylation (OXPHOS) is in excess of O2 delivery during whole-body exercise (5), and increases in VO2max with training are linked primarily to improved oxygen delivery and expansion of capillary volume, allowing for greater O2 diffusion (and extraction). Accordingly, there is strong evidence to support the hypothesis that, in healthy humans, muscle mitochondrial respiratory capacity poses no limitation to VO2max and always retains excess capacity over O2 delivery. However, changes in mitochondrial volume and regulation play a major role in enhancing submaximal endurance performance.
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However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. . ... A common hallmark of several neurodegenerative diseases (Huntington´s Disease, Alzheimer´s Disease and Parkinson´s Disease) is the impaired function or expression of PGC-1α, the master regulator of mitochondrial biogenesis. Among the promising strategies to ameliorate mitochondrial-based diseases these authors highlight the induction of PGC-1α via activation of PPAR receptors (rosiglitazone, bezafibrate) or modulating its activity by AMPK (AICAR, metformin, resveratrol) or SIRT1 (SRT1720 and several isoflavone-derived compounds).
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The beneficial effects of exercise extend beyond peripheral tissues to also include the brain. ... Because of the blood–brain barrier, it was traditionally thought that the beneficial effects of exercise on the CNS were not orchestrated through systemic changes in the periphery. However, recent studies suggest that the effects of exercise are, in part, mediated by changes in the systemic environment. Investigations looking at magnetic resonance imaging (MRI) measurements of cerebral blood volume in the hippocampus have demonstrated that exercise selectively increased the cerebral blood volume of the dentate gyrus, correlating with post-mortem increase in neurogenesis (Pereira et al. 2007). From a molecular perspective, elevated systemic levels of circulating growth factors such as vascular endothelial growth factor and insulin-like growth factor 1 (IGF-1) in blood elicited by increased exercise have been shown to mediate, in part, enhancements in neurogenesis (Trejo et al. 2001; Fabel et al. 2003). Coincidently, circulating levels of IGF-1 decrease with age and the restoration to levels resembling a younger systemic environment up-regulate neurogenesis and improve learning and memory (Lichtenwalner et al. 2001; Darnaudery et al. 2006).
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Physical fitness, achieved through regular exercise and/or spontaneous physical activity, can protect against the development of chronic stress- and inflammatory-related disease by optimizing physiological and neuroendocrine stress responsivity, promoting an anti-inflammatory state, and enhancing neuroplasticity and growth factor expression. stress responsive systems are adaptive when activated and terminated in a timely manner, prolonged (or insufficient) activation of these systems can cause a variety of maladaptive responses. ... For example, Rimelle et al.  documented significantly lower cortisol and heart rate responses to psychosocial stress (Trier social stress test) in trained men compared with untrained men. Moreover, significantly greater calmness and better mood, and a trend towards lower state anxiety, were noted in these trained men during the stress protocol. ... Whereas hippocampal and/or serum/plasma BDNF levels are downregulated by chronic psychosocial stress and inflammation [138,180,201], central and peripheral BDNF levels can be upregulated by acute exercise [33,198,202,203]. ... Exercise-induced increases in brain monoamines (norepinephrine and serotonin) may also contribute to increased expression of hippocampal BDNF . In addition, other growth factors—insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor—have been shown to play an important role in BDNF-induced effects on neuroplasticity [33,172,190,192], as well as exerting neuroprotective effects of their own [33,214,215], thereby contributing to the beneficial effects of exercise on brain health. Like BDNF, increases in circulating IGF-1 levels in response to acute exercise are only transient and possibly time-dependent as it relates to chronic training (i.e. increases seen after 12 weeks of training) . ... Whereas reduced HPA axis reactivity to a given stressor has repeatedly been reported in physically fit individuals, the finding of reduced sympathetic reactivity is less consistent.
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Exercise-related improvements in brain function and structure may be conferred by the concurrent adaptations in vascular function and structure. Aerobic exercise increases the peripheral levels of growth factors (e.g., BDNF, IFG-1, and VEGF) which cross the blood-brain barrier (BBB) and stimulate neurogenesis and angiogenesis (Trejo et al., 2001; Lee et al., 2002; Fabel et al., 2003; Lopez-Lopez et al., 2004).
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The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is not only involved in brain growth, development and myelination, but also in brain plasticity as indexed by neurogenesis. This may have links to various cognitive effects of GH and IGF-1. GH and IGF-1 affect the genesis of neurons, astrocytes, endothelial cells and oligodendrocytes. Specifically, IGF-1 increases progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex IGF-1 only affects oligodendrogenesis. ... Altogether, data suggest that both exogenous and endogenous GH and/or IGF-1 may be used as agents to enhance cell genesis and neurogenesis in the adult brain. ... GH and IGF-1 have been shown to affect a multitude of mechanisms, including neurogenesis, oligodendrogenesis, angiogenesis, glutamate receptor activation, cholinergic system, dopaminergic reward system, monoamine abundance, dendritic arborization, astrocyte communication via connexin 43, and opioid receptor abundance ... IGF-1 also reaches the brain via both the capillary bed BBB and via the blood-CSF barrier. It appears that IGF-1 uptake is mediated by a specific carrier both in the capillary bed BBB  and in the blood-CSF barrier [41, 42]. Moreover, IGF-1 transport across the BBB can be either increased, such as by exercise  ... Thus, although not fully characterized, there appear to be mechanisms for transport of both GH and IGF-1 across the BBB. ... Interestingly, exercise is a factor known to enhance cell genesis in the brain, and it appears that IGF-1 is a key mediator of the effect of exercise in terms of cell genesis in the adult brain [52, 53]. ... IGF-1 treatment enhances neurogenesis [52, 53, 55], oligodendrogenesis [56, 58] and angiogenesis . ... As physical exercise has positive effects in many diseases as well as in normal health, it is of interest that circulating IGF-1 as been shown to be one of the mediators of enhanced neurogenesis in the hippocampus.
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- Media related to Fitness training at Wikimedia Commons
- MedLinePlus's Topic on Exercise and Physical Fitness
- Science Daily's reference on Physical Exercise
- Guidance on the promotion and creation of physical environments that support increased levels of physical activity."Physical activity and the environment".