Diet and health
Much remains to be learned about the complex relation between nutrition, health, and disease. Dietary preferences are no less complex and individual. Despite these uncertainties, a dietary pattern characterized by a high intake of vegetables, fruits, legumes, whole grains, fish, and poultry is associated with major health benefits for men87 and women.30,88 Physicians have an important role in educating patients about healthful nutrition and providing dietary guidelines [see Table 5].
Numerous observational studies have demonstrated a dose-related inverse relation between habitual physical activity and the risk for many of the chronic illnesses that afflict people in industrialized societies.89 The protective effect of exercise is strongest against coronary artery disease but is also significant against hypertension, stroke, type 2 (non-insulin-dependent) diabetes mellitus, obesity, anxiety, depression, osteoporosis, and cancers of the colon, breast, and female reproductive tract. Despite these proven benefits, only 25% of adults in the United States exercise at recommended levels.90 Of all deaths in the United States, as many as 12%, or about 250,000 annually, can be attributed to a sedentary lifestyle.91
The physiologic effects of exercise depend on the type of exercise, its intensity, its duration, and its frequency.92 Exercise is either isometric or isotonic. Isometric contraction of muscle is characterized by an increase in muscle tension without a significant change in fiber length. No external work is accomplished, but substantial energy is expended. Examples of isometric work include handgrip exercises, pushing or pulling against a fixed resistance, and holding a heavy weight. In contrast, isotonic work involves a shortening of muscle fibers with little increase in tension; examples include swimming, bicycling, and running. Most exercise includes both isometric elements and iso-tonic elements.
Isometric and isotonic exercises differ substantially in their physiologic effects. Isometric work increases total peripheral resistance; both systolic blood pressure and diastolic blood pressure rise substantially, with relatively little increase in stroke volume or cardiac output. Isotonic work lowers total peripheral resistance, but heart rate and cardiac output rise. Systolic blood pressure rises substantially, but diastolic pressure changes little, resulting in a small increase in mean arterial pressure. Isometric work places a pressure load on the heart, whereas iso-tonic work imposes a volume load.
Isometric exercise increases muscle strength and bulk, which is desirable for competitive athletes, for patients recovering from musculoskeletal injuries, and for individuals who wish to attenuate the loss of muscle mass and bone strength that accompanies sedentary aging and certain chronic illnesses.93 However, static exercises produce minimal cardiovascular conditioning, and the circulatory demands of intense isometric work can be hazardous to patients with heart disease. In contrast, dynamic exercises enhance endurance and can produce adaptive cardiovascular changes in healthy individuals and cardiac patients.
Cardiovascular Response to Dynamic Exercise
The acute circulatory response to maximal dynamic exercise is a dramatic rise in cardiac output, from about 5 L/min to 20 L/min in healthy young men. The increased cardiac output results from a 300% increase in heart rate. This increased transport of oxygen is matched by a threefold increase in peripheral oxygen extraction. Total peripheral resistance falls, and blood is shunted away from nonworking muscles and the viscera toward exercising muscles and the coronary circulation, where blood flow increases fourfold.
The physiologic adaptations produced by repetitive dynamic exercise are known collectively as the training effect. The magnitude of the training effect depends on the intensity, duration, and frequency of exercise. Training requires rhythmic, repetitive use of large muscle groups for prolonged periods. Fitness can be developed and maintained in healthy adults with three to five exercise sessions a week. Each day’s exercise should involve isotonic work at 60% to 90% of maximal heart rate for 20 to 60 minutes, either continuously or in increments of 10 minutes or longer.94 Obviously, sedentary persons and patients with cardiopulmonary disease must initiate training at lower intensities and shorter durations and build up gradually.
Perhaps the most obvious training effect is resting bradycar-dia; heart rates of 40 to 50 beats/min are common in highly trained endurance athletes. The mechanisms responsible are not fully understood but probably involve increased vagal tone, decreased sympathetic activity, and increased stroke volume. The best overall measurement of the trainin. g effect and of physical fitness is the maximal oxygen uptake (VO2MAX).
Oxygen consumption relates directly to the amount of muscular work; maximal oxygen uptake therefore reflects m. aximal work capacity. Many factors determine an individual’s VO2MAX, including age, gender, lean body mass, genetics, and, most important, the level of habitual exerci.se. Just 3 weeks of bed rest will cause a 20% to 25% decline in VO2MAX. It is no wonder that patients are debilitated after being confined to bed by illness or treatment regimens. In c.ontrast, regular training lasting weeks or months will increase VO2MAX, typically by 30% to 40%.
Both central (cardiac) and peripheral (muscular) adaptations are involved in the training effect. In healthy individuals, training produces dramatic changes in cardiac structure. The dimensions of all cardiac chambers increase by up to 20%, and my-ocardial mass may increase as much as 70%.95 Although increased coronary blood flow and collateralization have not been demonstrated directly in humans, echocardiographic studies show that elite athletes have increased proximal coronary artery size, which is proportional to their increased left ventricular mass. Cardiac function is also enhanced by training; left ventricular contractility and stroke volume increase, and angiographic studies have demonstrated increased dilating capacity in the coronary arteries of endurance athletes. Exercise training also improves endothelial function in patients with coronary artery disease and in elderly persons.
In addition to these cardiac changes that allow enhanced oxygen delivery, there is improvement in peripheral oxygen extraction caused by enhanced O2 extraction by the skeletal muscles themselves. This effect on skeletal muscle is specific for the muscles that have been trained; if only leg muscles are trained, the circulatory response to strenuous leg exercise will improve, but the response to vigorous arm exercise will not change.
Exercise training decreases the risk of hypertension. A meta-analysis of 54 controlled intervention studies concluded that isotonic exercise training lowers both systolic blood pressure by about 4 mm Hg and diastolic blood pressure by about 3 mm Hg.98 Regular exercise can even reduce left ventricular hypertrophy and blood pressure in patients with severe hyperten-sion.99 Regular exercise also lowers catecholamine levels, protecting against arrhythmias, and it reduces myocardial oxygen demands.89
Although isotonic exercise reduces resting blood pressure, isometric exercise increases total peripheral resistance and acutely elevates blood pressure. However, sustained hypertension is not a complication of resistance training, which may even reduce resting blood pressure.100 Unsupervised isometric exercising should be avoided by patients with cardiovascular disease; with appropriate precautions, however, it can be safe for selected cardiac patients and can produce favorable effects on muscular function.
Except in people with intrinsic lung disease, the pulmonary diffusion capacity does not limit exercise. At heavy work loads, however, skeletal muscle oxygen demands exceed oxygen delivery. As a result, muscle metabolism becomes anaerobic; the lactic acid that accumulates is buffered by bicarbonate, so that the pH remains nearly normal. The CO2 that is liberated by the buffering reaction produces an increased ventilatory drive and tachypnea. Athletes know when they have crossed the anaerobic threshold by a markedly increased respiratory rate and a sensation of dyspnea. Habitual exercise does not improve pulmonary function in healthy people, but exercise training may be helpful in patients with chronic lung disease as a result of adaptations in muscles rather than in the lungs.
Isotonic exercises increase muscle endurance. Training increases capillary density, and it can increase muscle mitochondria and oxidative capacity more than twofold. These changes account for the greater oxygen extraction that is an important element of the training effect. Isometric training builds muscle mass, which improves performance and may decrease injuries. Isometric exercises involving slow repetitions of work against high resistance produce fiber hypertrophy and strength but do not alter muscle enzyme content.
Exercise training affects tissues in addition to muscles. Of great importance, weight-bearing exercises increase bone mineral density, reducing the risk of osteoporosis. Repetitive performance of athletic tasks improves coordination and efficiency; changes in neuromuscular recruitment may be partially responsible. Tendon strength and bone density increase as a result of repetitive use. Joint wear and tear remains a concern, but as long as there is no trauma, habitual exercise probably does not produce degenerative joint disease.102 In fact, aerobic and resistance exercise may help reduce disability in patients with os-teoarthritis and fibromyalgia.103,104
Figure 2 During exercise, catecholamine stimulation of adipose tissue rapidly mobilizes free fatty acids to achieve blood levels that are six times the normal level, which are far higher than the muscle can use. Glucose derived from the liver and muscle glycogen are initially phosphorylated to yield glucose-6-phosphate (G6P). The G6P, the free fatty acids from adipose tissue, and the muscle’s own triglycerides are metabolized to acetyl coenzyme A (acetyl CoA). This compound then undergoes oxidative metabolism in the mitochondrial Krebs cycle (blue), thus providing energy for exercising muscle.
Skeletal muscle contains only very limited energy stores; preformed adenosine triphosphate (ATP) and creatine phosphate (CP) can supply less energy than that which is consumed in a 100-yard dash. Clearly, ATP and CP must be generated during exercise. Only three sources of fuel are available to skeletal muscle for this purpose: endogenous muscle glycogen, blood glucose, and free fatty acids (FFAs) derived either from muscle triglyceride or from adipose tissue. Normally, the body’s skeletal muscle contains only 120 g of glycogen and the liver only 70 g. The 600 kcal of energy available from these two sources could sustain running for only 6 miles. The blood glucose provides only 40 kcal more. In contrast, the average person’s 15,000 g of adipose tissue provides 100,000 kcal of energy, theoretically enough to fuel a run from Boston to Atlanta.
At rest and during low-intensity exercise, both FFAs and muscle glycogen provide energy. As exercise begins, catecho-lamines stimulate adipose lipase, which cleaves triglyceride into glycerol and three FFA molecules [see Figure 2]. In muscle cells, FFAs are metabolized to acetyl coenzyme A (acetyl CoA); in the presence of oxygen, acetyl CoA undergoes oxidative metabolism by enzymes of the citric acid (Krebs) cycle in mitochondria.
As the intensity of exercise increases, the relative contribution of FFAs decreases and glycogen becomes more important, and at maximum work, muscle depends entirely on glycogen. When oxygen is available, glycogen is metabolized in the cytoplasm to pyruvate, which then undergoes oxidation in the mitochondria via the citric acid cycle to water and CO2. However, when the demands of muscle outstrip the availability of oxygen, energy can be generated only anaerobically via glycolysis. Anaerobic metabolism is much less efficient: from a gram of glycogen, anaerobic metabolism generates only 5% of the energy that aerobic metabolism generates. In addition, pyruvate cannot be converted to acetyl CoA. Instead, pyruvate is reduced to lactate. Acidosis limits muscular performance, and buffering by the bicarbonate system generates CO2, causing tachypnea.
Although the blood glucose itself constitutes only a modest caloric reserve, glucose turnover is greatly accelerated by exercise. During exercise, the liver releases glucose by both glyco-genolysis and gluconeogenesis. Simultaneously, peripheral glucose uptake is enhanced. As a result of these metabolic events, blood glucose can account for 10% to 30% of exercising muscle’s metabolic needs. The blood glucose level remains normal and may even rise during modest exertion. However, hypoglycemia can occur if hepatic glycogen stores are depleted and high-intensity exercise continues to consume blood glucose and muscle glycogen.
These changes in glucose metabolism are moderated by a number of hormonal alterations. Circulating catecholamines, growth hormone, cortisol, and glucagon levels rise. Insulin levels fall. All of these factors tend to elevate blood glucose levels. Glucose that is ingested during exercise will also tend to maintain blood glucose levels, but ingestion of glucose before exercise may actually raise insulin levels, thus impeding energy mobilization. Contrary to popular so-called instant-energy theories, preexercise meals should not contain concentrated sweets. Indeed, preexercise meals should be sparse, and people should probably ingest little other than water during the 2 hours before exercise.
Exercise increases the insulin sensitivity of muscle, thereby increasing glucose transport and muscle glycogen synthesis.
Even moderate physical activity such as walking can help prevent the development of type 2 diabetes mellitus105 and the metabolic syndrome.106 Because exercise improves glucose tolerance in diabetic patients, patients taking insulin may require special precautions to exercise safely [see Medical Complications of Exercise, below].
During exercise, the rate of protein synthesis is depressed. As a result, amino acids are available for anabolic processes, including hepatic gluconeogenesis. Amino acids also may directly provide a small fraction of the energy needed for muscle contraction. It is not clear whether athletes have higher nutritional protein requirements than sedentary persons; the ingestion of protein and amino acid supplements does not enhance athletic performance.
Regular aerobic exercise also alters body weight and body composition. If dietary caloric intake remains constant, exercise will produce slow weight loss.107 It takes 35 miles of walking or jogging to consume the calories present in 1 lb of adipose tissue. Intense exercise also stimulates both energy expenditure and lipid oxidation for up to 17 hours after exercise itself, thus further contributing to a reduction in body fat. Even as body fat declines, muscle mass increases; because muscle is denser than fat, net weight loss may be slight. Swimming appears to be less effective than land exercise for reducing body fat and increasing bone mineral content.
Effects on Blood Lipids
Exercise increases serum levels of HDL-associated cholesterol (HDL-C), probably by delaying hepatic HDL-C catabo-lism. The amount of exercise appears to be the major determinant of the magnitude of the increase in HDL-C. As little as 5 to 10 miles of jogging a week will elevate HDL-C levels, which rise with increasing exercise in a dose-response fashion; beyond about 35 miles a week, however, additional training does not produce a further increase in HDL-C levels.108 Similar changes in HDL-C levels have also been demonstrated in walkers, crosscountry skiers, tennis players, bicyclists, and other endurance athletes. The effects of exercise are independent of other factors known to alter HDL-C levels, such as diet, body weight, smoking, and alcohol consumption. Exercise must be sustained to maintain high HDL-C levels.
The effects of exercise on HDL-C levels are observed consistently, but changes in the other blood lipid levels have varied. In general, exercise produces a fall in triglyceride and chylomi-cron levels. Total cholesterol and LDL cholesterol levels also tend to decline. Heritable factors, in part, determine lipid profile responses to exercise.109
A mild decrease in hematocrit is commonly observed in endurance athletes. This so-called sports anemia is usually a pseudoanemia, because red blood cell mass is normal but plasma volume is increased; decreased viscosity has also been observed. Exercise-related hemolysis or gastrointestinal blood loss may be an additional factor in some cases of anemia in athletes. No consistent long-term changes in polymorphonuclear leukocytes, lymphocytes, or immunoglobulins have been noted.
Hemostatic mechanisms are influenced by exercise. Endurance exercise acutely increases fibrinolytic activity, and repetitive exercise is associated with reduced fibrinogen levels. In contrast, intense exercise can activate platelets,110 perhaps contributing to a prothrombotic state that may contribute to exertion-induced cardiac events111 [see Medical Complications of Exercise, below]. The effects of exercise on platelet function require further study.
Effects on Body Fluids
During exercise, skeletal muscle generates a tremendous amount of heat. Sweating is necessary to dissipate this heat. During strenuous exercise in a warm environment, up to 2 L can be lost each hour. Because sweat is hypotonic, the serum sodium concentration rises. Even in the absence of systemic acidosis, serum potassium levels may rise because of an efflux of potassium from muscle cells, but potassium levels normalize within minutes after exertion ceases.
The decline in blood volume, together with a shift in blood flow from the kidneys to skeletal muscle, produces a sharp decline in urine volume during exercise. The rise in plasma osmo-larity increases thirst. However, thirst lags behind volume requirements, and fluid intake is often inadequate during athletic events. Volume depletion impairs athletic performance and can contribute to renal dysfunction or heatstroke. Unfortunately, coaching lore often limits fluid intake for fear of cramps, when, in fact, athletes can tolerate large volumes of fluids during brief pauses in exercise. Although water is an excellent fluid replacement, excessive amounts during prolonged exercise can produce severe, even fatal, hyponatremia.112 Athletes do not require supplemental potassium or salt, so popular glucose-sodium-potassium solutions make little sense physiologically.
Endurance exercise produces improvements in mood, self-esteem, and work behavior both in healthy people and in patients undertaking cardiac rehabilitation; exercise training can help treat depression.113 Several mechanisms have been suggested to explain the psychological effects of exercise. Purely psychological factors, such as distraction, may be involved. The serum levels of ^-endorphin, monoamines, and other neu-ropeptides are affected by exercise in direct relation to the intensity and duration of exercise. Changes in endogenous opioid peptides may mediate the subjective effects of exercise (so-called runner’s high).
Exercise and the elderly
Many physiologic changes attributed to aging closely resemble those that result from inactivity.114 In both circumstances, bone calcium wastage occurs, and there are decreases in VO2MAX, cardiac output, red blood cell mass, glucose tolerance, and muscle mass; total peripheral resistance and systolic blood pressure are increased, as are body fat and serum cholesterol levels. Regular exercise appears to retard these age-related maladies. Exercise training improves left ventricular systolic function and increases stroke volume to maintain exercise cardiac. output in healthy, older people.115 The age-related decline in VO2MAX has been found to be twice as great for sedentary men. as for active men, and even low-intensity training can improve VO2MAX in the elderly. Exercise training also helps blunt the age-related decline in peripheral vascular function experienced by sedentary people. Endurance training improves glucose tolerance and serum lipid levels in older men and women, and regular exercise appears to blunt the age-related decline in resting metabolic rate. Physical activity in the elderly is associated with increased functional status and decreased mortality. Exercise is safe in the elderly if simple precautions are observed [see Prescribing Exercise, below]. Walking programs increase aerobic capacity in persons 70 to 79 years of age, with few injuries; healthy elderly persons who are randomly assigned to aerobic exercise acquire fewer new cardiovascular disorders than control subjects. Appropriate resistance weight programs are not hemodynamically stressful in the elderly and produce increases in muscle strength, functional mobility, and walking endurance. Even frail nursing home residents (mean age, 87 years) responded to resistance training with an increase in muscle mass and strength, as well as improved gait velocity, stair-climbing power, and spontaneous activity. Although more studies are needed to clarify correlations between aging, inactivity, and exercise, enough information is available to warrant a recommendation of carefully planned exercise programs for the elderly.