The Health Benefits of Exercise
The health benefits of exercise are many (
Table 8.1) and include improvements in virtually every organ system in the body. Some of these benefits are increased longevity and reductions in cardiovascular disease, myocardial infarction, congestive heart failure (CHF), stroke, hypertension, dyslipidemia, dysglycemia, obesity, thrombosis, cancer, immune function, infections, and gastrointestinal illness. Memory and central nervous system function improve with reductions in anxiety, stress, depression, disturbances in sleep, and more.
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2 Whether exercise is dynamic/isotonic, isometric, aerobic, anaerobic, based on oxygen utilization, there are specific benefits.
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5 Aerobic or endurance exercise (AE) imposes a volume overload on the cardiovascular system with increased VO2, heart rate, cardiac output, and stroke volume; reduced systemic vascular resistance; decreased diastolic blood pressure (BP); and increased A-VO2. Resistance training (RT) exerts both a volume and a pressure overload state with little change in heart rate, cardiac output, stroke volume, systolic or diastolic BP; it increases or does not change VO2.
3 The relative merits and specific combinations of interval and endurance aerobics and RT will be discussed in more detail later in this chapter.
Exercise Physiology and Theory
Skeletal muscle is a secretory (endocrine) organ, and exercise increases the metabolic and secretory/endocrine capacity of muscle.
1 Specific kinds of exercise can alter the ways genes function and interact with cells.
1 By triggering the right exercise-gene interactions, inflammation, oxidative stress, and immune dysfunction are improved.
1The slow physical deterioration of the cardiovascular system and body in general that is seen with age is not inevitable. It is largely the result of diet and movement—or the lack thereof. Movement is one of the primary keys to overall health and especially cardiovascular health. The movement required is the same kind of natural movement that kept humans in robust physical health for millennia. This is not the kind of exercise that most personal trainers, fitness enthusiasts, or doctors recommend. As a matter of fact, most doctors and trainers recommend the exact opposite approach to movement and exercise, one that may actually accelerate the deterioration of health, cardiovascular benefits, and overall aging. In this chapter, we will discuss the optimal type and duration of exercise required to improve health. It is important to avoid the overtraining syndrome that actually increases muscle breakdown, elevates cortisol levels and sympathetic tone, increases oxidative stress and inflammation, and results in the opposite effects of those noted in
Table 8.1.
The power of exercise is a function of the numerous hormones, cytokines, chemokines, interleukins, and other signaling molecules and mediators that are released with the proper type of exercise; these substances influence genes, inflammation, oxidative stress, and immune function. The effects of exercise on human genetics are shown in
Table 8.2.
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6 Exercise modifies the expression of at least 397 of 14,500 genes tested linked to energy metabolism upregulation, protein and amino acid dephosphorylation, heme biosynthesis, downregulation of protein catabolism, and the other effects shown in
Table 8.2.
6 Skeletal muscle has the ability to alter the type and amount of protein depending on the disruptions that occur in cellular homeostasis.
5 The exercise adaptation of skeletal muscle involves numerous signaling mechanisms that initiate replication of DNA genetic sequences that signal
RNA production of amino acids and proteins that peak about 3 to 12 hours post exercise.
5 Training volume, intensity, and frequency as well as the half-life of the proteins will determine the final functional outcomes of exercise.
5 Endurance training increases mitochondrial biogenesis, fast to slow fiber type transformation, and substrate metabolism, whereas heavy resistance exercise stimulates synthesis of contractile proteins to induce muscle hypertrophy and increase maximal contractile force.
5 Increased muscle cross-sectional area and altered neural recruitment patterns are the principal adaptations to repeated bouts of heavy resistance exercise. A balance of protein synthesis, protein degradation, and muscle remodeling also reduces atrophy pathways with a result net increase in protein synthesis and muscle hypertrophy with RT.
Signal Transduction Pathways in Skeletal Muscle: Muscle Molecules, Hormones, Other Mediators, and Myokines
Many of the health benefits of exercise are partly linked to reduced levels of inflammation and oxidative stress with chronic adaptive mechanisms. Optimal exercise regimens release numerous signaling molecules that stimulate healthy responses that include inflammation, anti-inflammation, oxidative stress, oxidative defense, proimmune and anti-immune mechanisms for muscle, and other organ repair, regeneration, and growth. Exercise, when performed properly, is the ultimate metabolomic and proteomic prescription to connect the internal weblike signaling within the human body. Hormones, myokines (cytokines specific to skeletal muscle), cytokines, nitric oxide, and other mediators of muscle have numerous functions in the body, including control of fuel mechanisms, reproduction, hunger, immune function, gene expression, and every other metabolic process in the body. Human physiology is designed around movement, with a variety of hormones being released by body movement that produce intracellular signaling. But not all exercise has the same effect on genetic signaling.
1The muscular Olympic sprinters and wiry and gaunt Olympic marathon runners are extremes of the exercise regimen. Both have low percentages of body fat, but the sprinters have even less. The key difference is that sprinters exercise in very short, all-out bursts of energy, whereas marathon runners exercise for hours at a slower, steadier pace.
Caloric expenditure is really just a side effect of exercise, inconsequential compared with the enormous release of hormones and other signaling substances that determine cell function. Although the short, intense activity of sprinting does not burn many calories, it triggers the release of anabolic hormones such as human growth hormone and testosterone. This hormonal mix elevates caloric consumption for hours and even days after the sprinter has stopped running. Long-distance running does not elicit the same effect. Instead, it leads to the production of a catabolic hormonal mix (such as cortisol elevations) that causes muscle wasting, inefficient metabolic processing, and physical decay. Higher-intensity exercise produces the most muscle signaling. Exercise using full body movements, incorporating great amounts of muscle, requiring a combination of strength and endurance and forcing the muscle to do a lot of work in a short amount of time results in powerful muscle-building, fat-burning, anti-inflammatory, and brain-stimulating effects.
The conversion of mechanical signals during muscular contraction into a molecular event involves primary and secondary messengers to activate or repress specific signaling pathways to regulate exercise-induced gene expression and protein synthesis and degradation.
5 The mechanisms include
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Interleukins, tumor necrosis factor (TNF)-alpha, nuclear factor (NF)-KB, and other cytokines (discussed in detail later).
Mechanical stretch: This activates calcineurin, MAPK, and IFG signaling pathways.
Calcium flux: Neural activation of skeletal muscle generates an action potential that releases calcium from the sarcoplasmic reticulum. The amplitude and duration of calcium flux is regulated by the duration and frequency of the contractile stimulus.
Redox state: The NAD/NADH ratio is the primary redox mechanism in skeletal muscle that results from glycolysis and lipolysis in the mitochondria. The high production of reactive oxygen species (ROS) with exercise is buffered by Gpx, Mn, SOD, and catalase. Oxidative stress helps modulate exercise-induced adaptive signaling by serving as a primary messenger on transcriptional regulation and DNA binding with NF-KB and AP-1, direct effects on mitochondrial metabolism, decrease in myofilament calcium sensitivity, and hormetic effects to increase oxidative defense.
Phosphorylation status: Changes in the AMP/ATP ratio initiate numerous downstream molecular events in muscle such as activation of AMPK.
AMPK serves a primary role as the energy sensing kinase in both RT and AE related to cellular AMP/ATP ratios. AMPK stimulates insulin-independent glucose uptake and fat oxidation and regulates protein synthesis and gene expression via insulin IGF pathways.
Calmodulin and calcineurin regulate gene expression of contractile and mitochondrial proteins, fiber type plasticity, fast-to-slow phenotype transformation and fiber growth, hypertrophy, and regeneration.
IGF is stimulated during exercise and relates to glucose uptake, glycogen synthesis, and cell growth and differentiation through TOR, FoxO-1, and Akt pathways.
Interleukin-10-Fat Burning and Anti-inflammatory
Interleukin (IL)-10 regulates the muscle’s current and future energy needs. It is the most powerful metabolic signaling agent released from muscle as soon as the muscle starts to contract and move. It is released in even greater amounts as the activity becomes more intense. IL-10’s actions decrease inflammation; increase serum testosterone, growth hormone, and fat metabolism; regulate glucose; reduce weight; increase lean muscle mass; optimize fuel metabolism; and reduce the risk of myocardial infarction and stroke.
Interleukin-15—Muscle Sparing and Fat Burning
The major task of IL-15, which is released primarily through weight training, is to regulate the breakdown of muscle tissue. It is a major factor in determining the body’s muscle-to-fat ratio, which is an important contributor to coronary heart disease (CHD). Unfortunately, most modern exercise regimens do not trigger the release of adequate amounts of IL-15, for they avoid the short bursts of intense energy expenditure needed to produce it in sufficient amounts.
Interleukin-8—Muscle Angiogenesis
IL-8 is synthesized in muscle whenever the muscle is forced to produce energy anaerobically. When this happens, the muscle releases IL-8, which results in angiogenesis in skeletal and cardiac muscle that improves muscles oxygenation. This is a remarkable example of exercise’s ability to mold metabolism.
Interleukin-6—Inflammatory or Anti-inflammatory Myokine?5-13
IL-6 is generally an inflammatory cytokine when released from nonskeletal muscle cells.
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13 However, when released in high concentrations from skeletal muscle in the absence of TNF-alpha and IL-1, it is anti-inflammatory by actually blocking both via IL-1ra (receptor to IL-1) and soluble TNFR (TNF-alpha receptors) and stimulating the release of IL-10. The amount of IL-6 released during exercise far exceeds the level of TNF-alpha.
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13 This low ratio may account for the anti-inflammatory effects. The amount of IL-6 released is dependent on the intensity of the exercise, amount of muscle being used, and liver and skeletal muscle glycogen, with 20- to 100-fold increases over rest. IL-6 circulates as a myokine to all organs such as brain, liver, adipose tissue, heart, and blood vessels to control fat and glucose metabolism with adipose tissue fatty acid oxidation and liver glycogenolysis. There is also a reduction in inflammation and immune function with a shift to TH2 dominance. Finally, there are alterations in cortisol and leukocyte levels, central nervous system function (appetite regulation, fuel regulation, and body composition), BP, cardiovascular disease (CVD), and cancer risk, as well as promotion of many other health benefits.
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TNF-Alpha
This is suppressed in both RT and AE programs, which improves insulin sensitivity, reduces inflammation, and improves anabolic effects as long as muscle has time to recover during exercise regimens and there is no overtraining, which could actually increase TNF-alpha.
Lactic Acid—Growth Promoter, Energy Enhancer
Lactic acid, also known as lactate, is not just a waste product but actually has several beneficial effects. One of the immediate effects of lactic acid is to balance the acid pH that accumulates as a result of intense movement. The burn during intense exercise, usually blamed on lactic acid, is really caused by the accumulation of toxic metabolic waste products, such as ammonia and hydrogen. Lactic acid buffers their effects and improves exercise performance.
Lactic acid functions like a hormone by stimulating the release of testosterone and growth hormone that induce anabolic effects for increased lean muscle mass and better strength and function. In addition, lactic acid signals the muscle cells to increase both the number and efficiency of mitochondria to increase ATP, reduce production of radical oxygen species, and increase burning of body fat.
Nitric Oxide
Nitric oxide (NO) has numerous beneficial effects, including reducing arterial inflammation and oxidative stress, vasodilation, lowering systemic vascular resistance (SVR) and BP, decreasing atherosclerosis and CHD, improving mitochondrial biogenesis, and inhibiting thrombosis, permeability, and abnormal growth of vascular tissue. NO production is largely controlled by the endothelial cells, but activated muscles also release NO, allowing blood vessels supplying the muscle to remain open to maintain blood flow.
Aerobic Exercise and Resistance Training
RT improves cardiovascular conditioning; increases basal femoral blood flow and vascular conductance, basal metabolic rate (BMR), quality of life, muscle strength, endurance, lean muscle mass, and insulin sensitivity; decreases the risk of metabolic syndrome; and reduces sarcopenia, body fat, and risk of osteoporosis.
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15 The increase in strength and endurance varies from 25% to 100%. The BMR increases 7.7% in both genders within 3 to 6 months following moderate- to high-intensity training.
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14 AE after RT rather than before RT can prevent deterioration of vascular function such as reduction in pulse wave velocity, brachial artery diameter, mean blood velocity, and blood flow.
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16 BP remains in an acceptable range as long as the one RM (repetition maximum) stays between 40% and 60%, but significant BP elevations occur at over 80% of one RM.
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17 As will be discussed later, this is the reason for the recommendation of RT before AE with a specific time relationship of two to one ratio of RT to AE.
The cardiovascular responses to exercise differ between RT and AE.
3 AE imposes a volume-overload state on the cardiovascular system with increased VO2, heart rate cardiac output, and stroke volume and acute increases in systolic BP (SBP) but no change or decrease in diastolic BP (DBP).
3 With prolonged AE, both SBP and DBP fall as there is decrease in SVR.
3 There is asymmetric left ventricular (LV) hypertrophy with AE.
3In contrast, RT is a pressure-overload state on the cardiovascular system with little increase in VO2, mild increase in cardiac output, increased heart rate, and acute increase in SBP and DBP, but SBP and DBP decrease with chronic RT.
3 There is symmetric LV hypertrophy with a change in the ventricular diameter.
3 RT improves cardiovascular function, overall metabolic state, and general quality of life. An increase in strength and endurance of 25% to 100% in both genders occurs in 3 to 6 months.
3 There is decreased adipose tissue; increased lean muscle mass, BMR, and bone mass; reduced oxidative stress with increased muscle antioxidants; reduced risk of metabolic syndrome and osteoporosis; and improvement in peripheral arterial disease (PAD).
3 RT also improves clinical symptoms in patients with CHF.
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18Both RT and AE prevent and treat hypertension; improve dyslipidemia, insulin resistance, metabolic syndrome, diabetes mellitus, and body composition problems; and reduce cardiovascular morbidity and mortality.
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22 In type 2 diabetes mellitus, the combined RT and AE reduced hemoglobin A1C by 0.34% compared with control or RT or AE alone.
19 In a controlled study, 357 males with essential hypertension were grouped into control, interval training (IT), or continuous training (CT) programs at 60% to 79% maximum heart rate (MHR) for 45 to 60 minutes three times per week over 8 weeks. Both the IT and CT resulted in significant reductions in SBP, DBP, heart rate (HR), pulse pressure (PP), and mean arterial pressure (MAP) and improved VO2 (
P < .05) compared with the control group.
21 BP was reduced by 16.4/4.01 mm Hg in the IT group and 13.94/7.41 mm Hg in the CT group, and HR fell 8 and 12 b/min, respectively. VO2 was significantly improved in the IT group by 13.85 mL/kg/min versus 7.99 in the CT group, which is consistent with other studies. The combination of AE and RT at an energy expenditure of 4200 kcal per week is superior to either AE or RT alone in reducing BP, achieving weight loss, improving body composition, increasing upper and lower body strength, and improving cardiovascular fitness (VO2 max), CVD, and CHD.
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25 Increasing energy expenditure over 4200 kcal per week did not result in any additional benefit in reducing the relative CHD risk and may actually increase the risk.
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