ExerciseNutrition and Health
Chapter 3 Exercise, Nutrition and Health ADRIANNE E. HARDMAN Introduction By virtue of its mass and unique potential to increase metabolic rate, skeletal muscle is man’s largest ‘metabolic organ’. Energy expenditure is increased profoundly during exercise with the body’s large muscles and individuals who engage regularly and frequently in such exercise have enhanced energy requirements. These are met through increased nutrient intake, particularly of carbohydrate, so that the relative contributions of macronutrients to energy intake may be altered. This in itself may constitute a more healthy diet but, in addition, the metabolic handling of dietary fats and carbohydrates is improved, changes which help reduce the risk of developing several chronic diseases, speciﬁcally atherosclerotic vascular diseases, non-insulin-dependent diabetes (NIDDM, also known as adult-onset or type II diabetes) and possibly some cancers (Bouchard et al. 1994). An example of an association between disease risk and energy turnover is given in Table 3.1, which shows average daily energy intakes in prospective studies of coronary heart disease (CHD). Men who subsequently had fatal attacks showed lower levels of energy intake than survivors, an apparent paradox in the light of the increase in CHD risk associated with overweight, obesity and the deleterious metabolic sequelae of these. One explanation is that the men with higher energy intakes were more physically active, and that their exercise afforded a level of protection against CHD, compared with more sedentary men who ate less. Thus, the transition from a sedentary to an active state is associated with a higher energy turnover, with important implications for the transport, storage and utilization of the body’s metabolic fuels. All of these are altered in the trained state such that regular exercisers experience a lower risk of what has been called ‘metabolic, hypertensive cardiovascular disease’. Higher energy turnover may also be associated with improved weight regulation because food intake appears to be more closely coupled to energy expenditure with more exercise. Rather than prolonging life, regular exercise protects against premature death, with an estimated increase in longevity in men on average of one or two years (Paffenbarger et al. 1986). Moreover, lower all-cause mortality has recently been reported for physically active women (Blair et al. 1996), although evidence is much less extensive. People who take exercise also maintain a better quality of life into old age, being less likely than sedentary individuals to develop functional limitations. This chapter will identify some of the health gains which accrue from the biological interactions between exercise and the body’s metabolism of dietary carbohydrate and fats. For discussion of the evidence for a speciﬁc role of diet in promoting health, the reader is referred to other sources (WHO 1990). 39 40 nutrition and exercise Table 3.1 Average daily energy intake (MJ) and future risk of coronary heart disease. Adapted from Wood (1987). Cohort Heart disease victims Survivors English banking and London bus workers Framingham, Massachusetts Puerto Rico Honolulu, Hawaii 11.11 12.00 9.91 9.30 8.99 10.97 10.02 9.70 Atherosclerotic vascular diseases Pathological changes to the arterial wall give rise to atherosclerotic plaques, complex structures which result from proliferation of the smooth muscle cells and collagen, with deposition of cholesterol-rich lipid. These probably begin as fatty streaks which develop when lipid-laden macrophages accumulate after the integrity of the endothelium is breached and blood components are exposed to collagen in the wall of the artery. The clinical outcome depends on the site(s) and extent of the lesion: in coronary arteries, myocardial blood ﬂow is reduced, leading to chest pain on effort (angina) and a risk of thrombotic occlusion (heart attack) and/or disturbances in the electrical coordination of contraction; blood supply to the limbs is impaired when the arteries supplying the legs are narrowed, imposing severe limits on walking capability; and stroke occurs when there is thrombolytic occlusion of a cerebral artery or a local haemorrhage from a vessel with atherosclerotic damage. Links with nutrition are clear from, for example, the association between levels of saturated fat in the diet and the risk of CHD. Coronary heart disease Epidemiological studies have shown signiﬁcant associations between indices of both physical activity (a behaviour) and physical ﬁtness (a set of characteristics arising from the regular pursuance of this behaviour) and risk of the commonest manifestation of atherosclerosis, CHD — a disease responsible for one in four male deaths and one in ﬁve female deaths in the UK in 1994. We must be careful in our interpretation of associations, however, because exercisers may be constitutionally different from sedentary people in ways which decrease the likelihood of their developing the disease. Complementary scientiﬁc evidence of plausible mechanisms has much to contribute and the role of exercise in this will be discussed later. More than 50 population studies have compared the risk of CHD in physically active men with that of their sedentary counterparts. Careful scrutiny of their ﬁndings shows that sedentary men experience about twice the risk seen in active men (see Whaley & Blair 1995). This relative risk is of the same order of magnitude as that associated with hypertension (systolic blood pressure > 150 mmHg vs. < 120 mmHg), smoking (≥ 20 cigarettes · day–1 vs. no smoking) and high serum total cholesterol levels (> 6.9 mmol · l–1 vs. £ 5.6 mmol · l–1). Estimates of the protective effect of exercise are highest in those studies with the soundest design and methodology and no study has found a higher risk in active men. The effect is independent of hypertension, smoking and high total cholesterol levels. Early studies compared groups of men with different levels of occupational work. For example, postal workers who walked and cycled delivering mail and dock workers with high levels of habitual on-the-job energy expenditure experienced less heart disease than colleagues in less physically demanding jobs. Leisure time physical activity has also been studied and an inverse, graded relationship between leisure time physical activity and CHD was found among graduates (alumni) of Harvard and Pennsylvania universities (Paffenbarger et al. exercise, nutrition and health 1986); the risk of ﬁrst attack was one quarter to one third lower in men who expended more than 8.36 MJ · week–1 (2000 kcal · week–1) in physical activity (sports, garden work, walking, stairclimbing, etc.) than in classmates whose exercise energy expenditure was lower, i.e. high total energy expenditure in exercise was a determinant of risk. By contrast, prospective study of English civil servants found no association between total exercise energy expenditure and risk of heart attack (Morris et al. 1990); only men reporting ‘vigorous’ exercise experienced a lower risk than sedentary men. Vigorous was deﬁned as exercise likely to involve peaks of energy expenditure of 31 kJ · min–1 (7.5 kcal · min–1) or more. This is about the rate of energy expenditure of a middleaged man of average weight during fast walking, so it is not surprising that men who reported that their usual speed of walking was ‘fast’ (> 6.4 km · h–1) experienced a particularly low rate of attack. Low rates were also reported for men who did considerable amounts of cycling. Increasingly, studies have measured physical ﬁtness rather than, or as well as, physical activity. Their ﬁndings are broadly similar, i.e. a two- to threefold increase in the risk of cardiovascular death in men when comparing the least ﬁt with the most ﬁt groups (Whaley & Blair 1995). The 41 limited data available suggest an effect of at least this magnitude for women. Given the diverse methodologies and cohorts studied, the clarity with which the inverse, graded relationship between level of physical activity or ﬁtness and risk of mortality from CHD emerges is noteworthy. Figure 3.1 summarizes the ﬁndings of seven studies in which either leisure time activity (questionnaire) or ﬁtness (laboratory exercise test) was assessed prior to a follow-up period of 7–17 years. The precise pattern differs between studies, but it is clear that, whilst men with only moderate levels of activity or ﬁtness experience some degree of protection, higher levels tend to confer greater protection. Some studies, however, suggest that the relationship may be curvilinear — CHD risk decreasing steeply at the lower end of the continuum, reaching an asymptote in the mid-range. Thus, for men in the age group most studied . (approximately 40–60 years), values for Vo2max. of around 35 ml · kg–1 · min–1 have been proposed as being sufﬁcient to confer a worthwhile — not necessarily optimal — decrease in risk; evidence for women is scanty, but a comparable value is probably at least 2 or 3 ml · kg–1 · min–1 lower. Two aspects of the evidence strengthen the argument that the relation of activity and ﬁtness with CHD risk may be causal. First, only current Reduction in coronary events/mortality 100 80 + 60 40 + + + + + Paffenbarger et al., 1986 Morris et al., 1990 Blair et al., 1989 Leon, 1991 Ekelund et al., 1988 Sandvik et al., 1993 Shaper & Wannamethee, 1991 20 0 Physical activity/fitness level Fig. 3.1 The relationship between the level of physical activity (Paffenbarger et al. 1986; Ekelund et al. 1988; Morris et al. 1990; Leon 1991; Shaper & Wannamethee 1991) or ﬁtness (Blair et al. 1989; Sandvik et al. 1993) and risk of coronary heart disease among men in prospective studies. Adapted from Haskell (1994). 42 nutrition and exercise and continuing activity protects against heart disease; men who were active in their youth but became sedentary in middle-age experience a risk similar to that of men who had never been active. Second, men who improved either their physical activity level or their ﬁtness level between one observation period and another some years later experienced a lower risk of death than men who remain sedentary. To put these levels of risk reduction into perspective, taking up physical activity was as effective as stopping smoking. The role of exercise intensity in determining CHD risk is still uncertain. Several key studies have shown substantial reductions in risk with accumulation of physical activity, most of which was at a moderate intensity (see Haskell 1994). However, other evidence argues that more vigorous physical activity may provide unique beneﬁts. These uncertainties should not, however, detract from the wealth of evidence, gathered over a long period and in different populations, that identiﬁes physical inactivity as a major risk factor for CHD. Mechanisms by which exercise might confer a lower risk of CHD include effects on blood pressure, weight regulation, lipoprotein metabolism and insulin sensitivity — all of which are discussed below. Another suggestion, arising from the evidence referred to above that only current exercise protects against CHD, involves an effect on the acute phase of the disease — the thrombotic component, for example. This possibility is supported by associations between exercise habits and haemostatic factors and is an area justifying more research. Stroke Atherosclerotic damage to cerebral arteries is a prominent feature of stroke, so an effect of habitual exercise on the risk of having a stroke is plausible, but there is little direct evidence. In the British Regional Heart Study (Wannamethee & Shaper 1992), the age-adjusted rate for strokes showed a steep and signiﬁcant inverse gradient with physical activity category in men with or without heart disease or stroke at baseline; the risk in moderately active subjects was less than half that reported for inactive men. Data from the Honolulu Heart Program (Abbott et al. 1994) show an association between the risk of stroke and a physical activity index in older middleaged men (55–68 years) but not in younger men (45–54 years); the excess incidence of haemorrhagic stroke in inactive/partially active men was three- to fourfold. For thromboembolic stroke, among non-smokers the risk for inactive men was nearly double that for active men but there was no effect in smokers. Hypertension About 16% of men and 14% of women in England have hypertension (systolic blood pressure > 159 mmHg and/or diastolic > 94 mmHg). It is a major public health problem; even mild to moderate elevations in blood pressure substantially increase the risk of developing CHD, stroke, congestive heart failure and intermittent claudication in both men and women. There is some evidence that high levels of physical activity decrease the risk of developing hypertension (see Paffenbarger et al. 1991). For example, of 5500 male Harvard alumni free of hypertension at entry to the study, 14% developed the disease during 14 years’ observation. Contemporary vigorous exercise alone was associated with lower incidence, chieﬂy among men who were overweight-for-height. Similar conclusions arise from study of ﬁtness levels in relation to risk of hypertension: during follow-up of 6000 men and women over 1–12 years (median, 4) the risk of developing hypertension was 1.5 times greater for those with low ﬁtness (the bottom 75% of the sample) than for those deemed to have high ﬁtness (the top 25%). The rationale for a role for exercise in the prevention of hypertension is that, during exercise, there is marked dilation of blood vessels in active skeletal muscle, decreasing resistance to ﬂow. This persists during the recovery period, possibly contributing to the chronic lowering of (arterial) blood pressure which is often associated exercise, nutrition and health with regular aerobic exercise. The proposition that exercise brings blood pressure down has been tested experimentally. Valid conclusions can only be drawn from studies including nonexercising control subjects, because blood pressures tend to fall with repeated measurements when people become accustomed to the procedure. Controlled exercise intervention trials have found an average reduction of 3/3 mmHg (systolic/diastolic) in normotensives, with somewhat greater reductions in borderline hypertensives and hypertensives, i.e. 6/7 mmHg and 10/8 mmHg, respectively (Bouchard et al. 1994). These conclusions are based on resting blood pressure measured in clinic or laboratory; reductions in measures made during the normal living conditions tend to be less consistent and smaller but more evidence is needed. Moderate . intensity training (< 70% Vo2max.) leads to reductions in systolic blood pressure which are up to 40% greater than those resulting from training at higher intensity, possibly because of the lesser response of the sympathetic nervous system. The blood-pressure lowering effect of exercise probably occurs very rapidly, possibly after as little as 1 week of exercise training. Repeated short-term effects during recovery from individual exercise sessions may therefore be important. For example, in sedentary hypertensives, blood pressure is reduced for up to 8–12 h after a single exercise session. Longer training programmes produce somewhat larger reductions in blood pressures, however, suggesting that adaptive effects of habitual exercise, i.e. training, may act synergistically to enhance short-term effects. Glucose/insulin dynamics Diabetes mellitus afﬂicts about 2% of individuals in Western populations. By far the most common type is NIDDM, the incidence of which rises steeply with age. It is characterized by the failure of insulin to act effectively in target tissues such as muscle, liver and adipose tissue. The pancreas responds with enhanced secretion by its b-cells and plasma insulin levels are chronically high. Glucose intolerance (an abnormally high blood 43 glucose response to a standard 75 g oral load) develops gradually, fasting plasma glucose and insulin levels rising in parallel until the former reaches 7–8 mmol · l–1 (compared with normal values of around 4–5 mmol · l–1). At this stage the b-cells of the pancreas fail to maintain adequate insulin secretion and so there is a progressive fall in the fasting concentration. Profound glucose intolerance then develops and the condition worsens to overt NIDDM, the severity of which is determined by the inadequacy of b-cell function. Resistance to insulin-stimulated glucose uptake is the most important precursor of NIDDM and a common characteristic occurring in approximately 25% of the population. It is a prominent feature of obesity. Normal glucose tolerance is maintained but at the expense of hyperinsulinaemia, which leads to multiple derangements of metabolism — for example, high plasma levels of triacylglyceride (TAG) and low levels of high-density lipoprotein (HDL) cholesterol. In the longer term, these result in damage to blood vessels, with increased risk of developing CHD, hypertension and problems of the microcirculation, including renal disease and retinal damage. Risk of NIDDM Prospective studies show an inverse relationship between energy expenditure in leisure time activity and the risk of subsequently developing NIDDM (Kriska et al. 1994). For example, among male ex-students of the University of Pennsylvania the incidence of NIDDM decreased by some 6% for each 2.1 MJ (500 kcal) expended per week in physical activity. US male physicians who exercised ‘vigorously’ at least once per week experienced only 64% of the risk of developing NIDDM, compared with those who exercised less frequently. Findings have been similar for middle-aged women, those taking part in vigorous exercise experiencing only two thirds of the risk seen in other women. There are indications that the inﬂuence of physical activity may be particularly strong in those who are overweight. 44 nutrition and exercise Potential mechanisms The primary targets for insulin-stimulated glucose disposal are skeletal muscle and adipose tissue and inﬂuences on their glucose transport and metabolism dictate whole-body responsiveness to insulin. Muscle, representing some 40% of body mass, is probably the more important tissue. Insulin-mediated glucose uptake into skeletal muscle proceeds by a series of steps, the ﬁrst of which is insulin binding to receptors on the outer surface of the cell membrane. Glucose transport is achieved via ‘facilitated diffusion’, a process which involves a mobile protein carrier (GLUT4) which facilitates its transport across the membrane and is thought to be rate-limiting. Besides its action on glucose transport, insulin inhibits glycogenolysis, promoting glycogen synthesis. Muscle glycogen is reduced during exercise, creating the need for enhanced uptake and storage and raising the possibility that improved responsiveness of this tissue to insulin might exert an important inﬂuence on the body as a whole, explaining the lower incidence of NIDDM in physically active people. It is more than 25 years since the ﬁrst report of markedly lower plasma insulin concentrations in endurance-trained middle-aged men — both in the fasted state and after an oral glucose load — than in comparable sedentary men. These ﬁndings have generally been interpreted as a sign of increased insulin sensitivity in peripheral tissues, since hepatic glucose output is suppressed after glucose ingestion. Later studies have conﬁrmed this, measuring reduced insulin secretion and a shift in the insulin/glucose disposal response curve, promoting glucose transport and storage. Whole-body non-oxidative glucose disposal during glucose infusion is higher in endurance-trained athletes than in sedentary controls. Total activity of glycogen synthase and insulin-stimulated activation of the enzyme is enhanced as trained muscle adapts to the increased intracellular availability of glucose by developing an enhanced capacity for glucose storage as glycogen. The mechanisms by which training enhances glucose uptake in skeletal muscle are local rather than systemic and probably involve changes in levels of the muscle glucose transporter GLUT-4. Endurance-trained athletes possess higher levels of GLUT-4 than sedentary controls and levels are markedly higher in trained than in untrained muscle from the same individual, in association with a higher insulin-stimulated glucose uptake. Glucose uptake depends on its rate of delivery to the tissue, however, as well as that tissue’s responsiveness to insulin. Insulin stimulates increases in blood ﬂow to muscle in a doseresponsive manner and this effect could, speculatively, be enhanced in athletes because of improved capillarization. Following each exercise session, glucose uptake into skeletal muscle increases. This is partly an insulin-independent contractile effect which persists for several hours afterwards but, in addition, the response to insulin of the glucose transport system is improved. This usually lasts longer, for at least 48 h. As stated above, these may be responses to the need to replenish muscle glycogen; certainly exhaustive, intermit. tent glycogen-depleting exercise at 85% Vo2max. results in increased non-oxidative glucose disposal when measured 12 h later. When endurance-trained people refrain from training, their enhanced insulin action is rapidly reversed. The timescale of this reversal is not clear; training effects have been reported to persist for as little as 36 h but more typically for about 3 days, so that levels seen in sedentary people are approached within 1 week. Could the good insulin sensitivity which characterizes athletes be attributable to residual effects of their last training session, rather than to any long-term adaptive effects? The answer to this question is ‘probably not’. Studies have compared the response of a trained leg to a single session of exercise with that of an untrained (contralateral) leg to identical exercise; insulin action was improved in the trained leg but there was no effect in the untrained leg. The effect of training on insulin-mediated glucose disposal in muscle has therefore been described as a genuine adaptation to training — but short-lived. Whole-body insulin sensitivity is directly and exercise, nutrition and health positively related to muscle mass and, long-term, there may be additional effects of regular activity if muscle mass increases. By contrast with the effects of endurance training, which leads to predominantly qualitative changes in muscle insulin/glucose dynamics, the main effect of strength, and perhaps sprint, training may be to increase the quantity of muscle. Indeed, increases in lean body mass gained through strength training have been reported to be closely related to reductions in the total insulin response during an oral glucose tolerance test. Net effect of training Laboratory study has shown that exercise increases insulin sensitivity and decreases glucose-stimulated b-cell insulin secretion. It does not follow, however, that training spares insulin secretion and blood glucose levels in real life because training necessitates an increase in food intake. A study from Copenhagen makes the point well (Dela et al. 1992). These workers compared trained male athletes with untrained controls during their (different) ordinary living conditions as well as in the laboratory (Table 3.2). The higher daily energy intakes of the athletes — mean of 18.6 MJ · day–1 (4440 kJ · day–1), compared with 12.5 MJ · day–1 (2986 kcal · day–1) for the 45 sedentary men — reﬂected mainly differences in carbohydrate intake (678 vs. 294 g · day–1). Following oral glucose loads comprising identical fractions of daily carbohydrate intake, the areas under the plasma glucose and insulin concentration vs. time curves did not differ between athletes and untrained men. The two groups also had identical 24-h glucose responses during a day when they went about their normal activities (including one or two training sessions for the athletes). It seems that training, rather than sparing the pancreas, elicits adaptations in the action of insulin which allow the necessary increases in food intake without potentially harmful hyperglycaemia and overloading of bcells. During the day of normal activity, arterial insulin concentrations were, however, some 40% lower (NS) in athletes because of enhanced hepatic clearance. As insulin may directly promote both atherosclerosis and hypertension, a lower circulating level of the hormone may in itself be advantageous. The example just presented is an extreme case, with the athletes (one 800-m runner, one 1500-m runner and ﬁve triathletes) consuming some 50% more food energy than the sedentary comparison group. It is not atypical, however, as other researchers have found almost 80% of the increased energy intake associated with high Table 3.2 Integrated glucose and insulin responses to the same absolute oral glucose load (1 g · kg-1 body mass), to the same relative oral glucose load (27.7% of usual daily carbohydrate intake) and to food consumed under ordinary living conditions during a 24-h period. Adapted from Dela et al. (1992). Glucose Insulin (mmol · l-1 · 3 h-1) (pmol ·ml-1 · 3 h-1) Same absolute load Untrained Trained 1277* 1040 58* 24 Same % daily carbohydrate intake Untrained (1 g · kg-1 body mass) Trained (2.3 g · kg-1 body mass) 1277 1173 58 44 (mol · l-1 · 24 h-1) (pmol · ml-1 · 24 h-1) 24-h responses, ordinary living Untrained Trained *Signiﬁcantly different from trained, P < 0.05. 7.3 7.4 175 124 46 nutrition and exercise volume training was from carbohydrate. Similar, if smaller, effects on carbohydrate intake also tend to occur with more modest, non-athletic, levels of exercise. For example, when a group of middle-aged men took up jogging, their average daily energy intake increased by about 1.25 MJ · day–1 (300 kcal · day–1) after 2 years (12.5%) and this was almost all from carbohydrate (an increase of 70 g · day–1, about 30%) (Wood et al. 1985). Lipoprotein metabolism The body’s major energy store is TAG, a hydrophobic molecule which is transported through the watery plasma in particles called lipoproteins. Lipoproteins comprise a core of fatty material (cholesteryl esters as well as TAG) surrounded by a relatively hydrophilic coat comprising phospholipid, free cholesterol and one or more protein molecules known as apolipoproteins. The main categories are (in order of increasing density): chylomicrons, very low density lipoproteins (VLDL), low-density lipoproteins (LDL) and HDL. A brief outline of their metabolism helps understand both the inﬂuence of exercise and the potential implications for health. The function of chylomicrons is to carry TAG and cholesterol derived from the diet. Their main role is to deliver TAG to peripheral tissues and cholesterol to the liver. Secreted by the cells of the intestinal wall, they enter the bloodstream via the lymphatics. As they pass through the capillary beds of adipose tissue and muscle, their TAG is hydrolysed by the enzyme lipoprotein lipase (LPL), the non-esteriﬁed fatty acids (NEFA) released mostly being taken up by the tissues. As TAG is lost, the chylomicrons shrink and cholesterol-rich remnant particles are removed by hepatic receptors. By contrast, VLDL distribute TAG from the liver to other tissues. Like chylomicrons, they are a substrate for LPL and become TAG-depleted as they pass through capillary beds. Their remnants are LDL which carry (in ester form) some 70% of the cholesterol in the circulation, delivering it to a variety of tissues, according to their needs. Plasma total cholesterol concentration, in epidemiological study shown to be strongly and positively related to the risk of CHD, predominantly reﬂects LDL cholesterol. HDL provide a means by which cholesterol is routed from peripheral tissues to the liver where it is disposed of safely, mainly via synthesis into bile acids. HDL receive unesteriﬁed cholesterol which is released as excess surface material during the degradation of TAG-rich particles, but also incorporate cholesterol from the body’s cells when this is present in excess of needs. This pathway has been termed ‘reverse cholesterol transport’ and may be the mechanism underlying the inverse relationship between HDL cholesterol and the risk of CHD. In women, for example, an increase of 0.26 mmol · l–1 (about 20%) in HDL cholesterol is associated with a 42–50% decrease in CHD risk. An alternative explanation is that low HDL-cholesterol may be a marker for some defect in the metabolism of TAG-rich lipoproteins which means that chylomicron remnants and LDL remain in the circulation for longer, becoming correspondingly smaller and more readily taken up into atherosclerotic lesions. There is clear evidence of this for LDL, but also increasing awareness that the chylomicron remnant may also be atherogenic, not least because it may contain 30 times as many cholesterol molecules as a typical LDL particle. The view that atherogenesis is a postprandial phenomenon is gaining support and patients with known coronary artery disease show a more marked and prolonged rise in plasma TAG concentrations following an oral fat load than healthy controls. Insulin plays an important role in fat metabolism, coordinating events during the postprandial period. LPL activity in adipose tissue is stimulated and mobilization of NEFA is depressed through inhibition of hormone sensitive lipase and plasma NEFA levels fall markedly. When insulin sensitivity is poor, fat metabolism is disordered: there is failure to stimulate LPL, so TAG-removal rate falls; failure to sup- exercise, nutrition and health press release of NEFA from adipose tissue, leading to high plasma levels; and inappropriate hepatic VLDL secretion which exacerbates the rise in plasma TAG. Remnant particles of the TAG-rich lipoproteins persist in the circulation for longer, their smaller size increasing their atherogenic potential. Thus, insulin resistance may lie at the heart of the abnormalities of lipoprotein metabolism which are key features of the ‘metabolic syndrome’, i.e. low HDL cholesterol, high TAG levels and possibly also a preponderance of small dense LDL. It is not entirely clear, however, which is the ‘chicken’ and which the ‘egg’ here because an argument may be advanced for an underlying role of abnormal fat metabolism — secondary to the excessive delivery of TAG to adipose tissue and muscle — in the pathogenesis of insulin resistance. Either way, exercise may be beneﬁcial because of its potential to improve fuel homeostasis through its effects on the assimilation, mobilization and oxidation of fat fuels. Alterations to lipoprotein metabolism result. Effects of physical activity Well-trained endurance runners, men and women, possess lipoprotein proﬁles consistent with a low risk of CHD (Durstine & Haskell 1994). HDL cholesterol is typically 20–30% higher than in comparable sedentary controls. Triglycerides are low, particularly when veteran athletes (> 40 years) are studied. Total cholesterol concentrations stand out as low only when the control group is large and representative of the wider population. Athletes trained speciﬁcally for strength and power do not differ from sedentary individuals in these ways. Less athletic, but physically active, people also show lipoprotein proﬁles which are consistent with a reduced risk of cardiovascular disease. For example, data from the Lipid Clinics Prevalence Study showed that men and women who reported some ‘strenuous’ physical activity generally had higher HDL cholesterol levels than those who reported none (Haskell et al. 1980). Differences were independent of age, body 47 mass index, alcohol use and cigarette smoking. Even simple exercise like walking has been linked to elevated HDL levels, with relationships between distance walked per day and the concentration of HDL2, the subfraction that accounts for most of the difference in total HDL cholesterol between athletes and controls. In addition, men and women who habitually walk 12– 20 km · week–1 are only half as likely to possess an unfavourable ratio of total to HDL cholesterol (> 5) as a comparable no-exercise group. Thus cross-sectional observations of ordinary men and women, and of everyday activity, provide a basis for proposing that endurance exercise inﬂuences lipoprotein metabolism. Longitudinal studies are less consistent but, for HDL cholesterol, the consensus is that, over months rather than weeks, endurance exercise involving a minimum expenditure of about 15 MJ · week–1 (3580 kcal · week–1) causes an increase and that the magnitude of this tends to be greater when there is weight loss. The majority of longitudinal studies have employed rather high intensity exercise, most frequently jogging/running, but evidence is gradually becoming available that more accessible, self-governed exercise regimens may also be effective (Després & Lamarche 1994). For example, in previously sedentary middle-aged women who had rather low levels of HDL cholesterol (mean, 1.2 mmol · l–1) at base line, walking briskly for about 20 km · week–1 over a year resulted in a 27% increase. Increases in HDL cholesterol do not always mirror changes in ﬁtness, however. Figure 3.2 shows the main ﬁndings of one study which examined the effect of the intensity of walking in women over 24 weeks; fast walking at 8 km · h–1 produced greater improvements in ﬁtness than walking the same distance at slower speed, but increases in HDL cholesterol did not differ between groups walking at different speeds. Several other studies have conﬁrmed these ﬁndings. Dietary modiﬁcations recommended to overweight people invariably combine energy intake restriction with decreases in the intake of saturated fats and cholesterol. Such changes can 48 nutrition and exercise 6 +16% . ∆ VO2max (ml.kg–1.min–1) 4 +9% 2 +4% ∆ HDL cholesterol (mmol.l–1) 0.12 0.09 +6% +6% 0.06 +4% 0.03 +1% 0 0 –2 –6% –4 Controls Strollers Brisk walkers Fast walkers (a) Controls Strollers Brisk walkers Fast walkers (b) . Fig. 3.2 Changes in (a) maximal oxygen uptake (Vo2 max.) and (b) serum high-density lipoprotein (HDL) cholesterol concentration in control subjects (n = 10/13) and in three groups of previously sedentary women who walked 4.8 km · day–1 for 24 weeks. One group walked at 4.8 km · h–1 (n = 17/18, strollers), one group at 6 km · h–1 (n = 12, brisk walkers) and one group at 8 km · h–1 (n = 13, fast walkers). Adapted from Duncan et al. (1991). reduce HDL levels and, given the inverse association between HDL cholesterol and the risk of CHD, theoretically may diminish the anticipated beneﬁcial effects of decreased low density lipoprotein cholesterol. Exercise may be one way to offset a diet-related fall in HDL cholesterol. Comparison of two different interventions in sedentary overweight men and women, i.e. a low energy, low fat diet alone with the same diet plus exercise (brisk walking and jogging) showed that the addition of exercise to the low fat diet resulted in more favourable changes in HDL cholesterol than diet alone; in men, diet plus exercise provoked in a greater rise in HDL cholesterol than did diet only; and in women only the diet-plus-exercise group showed a favourable change in the ratio of LDL cholesterol to HDL cholesterol. It was mentioned above that changes in lipoproteins tend to be greater when an exercise regimen is accompanied by weight loss. There is also an effect which is independent of weight change, which appears to be linked to adaptations in skeletal muscle. During exercise there is a net efﬂux of HDL2 across a trained leg, but not across the contralateral untrained leg (Kiens & Lithell 1989). The rate of HDL2 synthesis is positively and strongly related to the rate of VLDL degradation. As the rate-limiting step in VLDL degradation is LPL activity, this points to skeletal muscle LPL as an important determinant of the effects of exercise on lipoprotein metabolism. Postprandial lipoprotein metabolism High levels of muscle LPL activity, leading to an enhanced metabolic capacity for TAG may therefore explain the elevated HDL cholesterol levels in physically active people. Endurance trained men and women show high levels of plasma and muscle LPL activity, together with high rates of TAG clearance (compared with sedentary con- exercise, nutrition and health trols). The high LPL levels probably arise from enhanced capillarization in the muscle of athletes because the enzyme is bound to the luminal surface of capillary endothelium. There are also short-term effects of recent exercise on postprandial TAG clearance. During recovery TAG clearance rates are increased, reducing the postprandial rise in plasma TAG concentration. The effect is greater after moder. ate intensity exercise (60% Vo2max.) than after low . intensity exercise (30% Vo2max.) of the same duration probably because of its greater energy expenditure; if energy expenditure is held constant the effects on lipaemia of low and moderate intensity exercise are strikingly similar (Tsetsonis & Hardman 1996). These short-term beneﬁts may therefore be potentially greater for trained . people because their higher Vo2max. values and greater endurance capability allow them to expend more energy than untrained individuals before becoming fatigued. People spend the majority of their lives in the postprandial state and exercise-induced decreases in postprandial lipaemia may be clinically important in the long term. When TAG clearance is good, the postprandial rise in TAG is reduced and TAG-rich particles will remain in the circulation for shorter periods, decreasing the atherogenic stimulus. Clinical evidence is consistent with this view because case-control studies have shown that postprandial TAG levels accurately predict the presence or absence of coronary artery disease. Energy balance In the UK, overweight (body mass index 25–30 kg · m–2) and obesity (body mass index > 30 kg · m–2) are a serious problem. More than 50% of men and more than one third of women in the age group 45–54 are overweight, whilst nearly 20% of both sexes are obese. Figures are even worse in the US, where mean body weight increased by 3.6 kg between 1976/80 and 1988/91. The health hazards of carrying excess weight are well documented so its prevalence rightly gives rise to concern. Recent ﬁndings 49 have particularly emphasized the importance of the regional distribution on body fat in relation to the risk of atherosclerotic metabolic disease. As with so many aspects of human health, there is substantial genetic control but environmental factors — diet, physical activity — modify these inﬂuences profoundly. The energy stores of the body are, of course, determined by the balance between energy intake and energy expenditure and any exercise contributes to energy expenditure. Although for most people the expenditure in habitual exercise rarely accounts for more than 20% of the total, physical activity is the only way in which energy expenditure can be increased voluntarily. Its importance in helping to control body weight and body fat content — for individuals or for populations — is still a matter of debate, despite the fact that there is a fairly consistent negative relationship between level of activity and body mass index or skinfold thicknesses. The energy stored in 1 kg of adipose tissue is approximately 32.4 MJ (7740 kcal). Energy expenditure during weight-bearing activities depends on body mass; for example, walking or running 1.6 km expends (net) about 220 kJ (52 kcal) for a 50-kg person, but about 350 kJ (84 kcal) for an 80-kg person, i.e. about 4.2 kJ · kg–1 body weight · km–1 (1 kcal · kg–1 body weight · km–1). Theoretically, therefore (and disregarding the small postexercise elevation of metabolic rate which, in non-athletes, probably never exceeds 10% of exercise expenditure), walking an extra mile every day for a year would expend (net) an estimated total of 80–128 MJ (19 100–30 580 kJ), i.e. the energy equivalent of 2.5–4 kg of adipose tissue. Resting metabolic rate decreases, however, as body mass falls and energy intake will be stimulated, offsetting this deﬁcit. As planned exercise increases, there may also be a spontaneous decrease in the physical activities of everyday living. The situation is far from simple. What tends to happen in practice? The consensus in the literature is that relatively small increases in physical activity (for example, walking 3.2 km · day–1, three times per week, adding up to 2.1–2.5 MJ or 500–600 kcal gross) are 50 nutrition and exercise not associated with changes in body fatness over 3–6 months (Haskell 1991). Above this amount of exercise, there tends to be a consistent loss of body fat, 0.12 kg · week–1 for men (a little less for women), total exercise energy expenditure being the variable most strongly related to the body mass change. Thus, the natural adjustments to increased exercise levels reduce, but do not eliminate, the theoretical energy deﬁcit. For example, in a study where sedentary men followed a programme of jogging for 2 years with no instructions about dietary intake, energy intake rose over the ﬁrst 6 months by about 1.3 MJ · day–1 (310 kcal · day–1). This compensation, however, did not increase further, remaining less than the energy expenditure of exercise so that a gradual loss of body fat occurred. Physical activity is increasingly viewed as an important adjunct to restriction of dietary energy. For example, the addition of exercise to a low energy diet has been reported to enhance weight and fat loss and prevent a fall in resting metabolic rate and it may also help with the intractable problem of weight maintenance after weight loss. The most important role for activity is probably that which is least well explored, i.e. prevention of weight gain. Some information on the relationship of activity with longer-term weight change in the general population is available from the NHANES-I Epidemiologic Follow- up Study in the USA; this found that the risk of major weight gain (> 13 kg) over a 10-year period was twice as high among inactive men and sevenfold higher among inactive women, compared with men and women of high activity level (Williamson et al. 1993). Exercise may inﬂuence the distribution of body fat as well as the amount. In population studies, individuals practising vigorous activities on a regular basis have lower waist-to-hip ratios than others, even after the effect of subcutaneous fat is adjusted for. Training has sometimes been reported to decrease this ratio even in the absence of a reduction in body weight. One reason may be that the metabolic state of the visceral fat depot is such that it should be readily mobilized during weight loss. For individuals who are overweight, the health gains from increased physical activity should not be judged solely by the extent of change in body fatness; several prospective studies have shown that overweight men and women who are physically active have lower rates of morbidity and mortality than comparable sedentary people. Fat balance The energy balance equation (change in energy stores = energy intake – energy expenditure) has Fig. 3.3 Sport offers an opportunity to people who wish to take exercise for health reasons rather than as a competitive outlet. Photo courtesy of Ron Maughan. exercise, nutrition and health traditionally provided the theoretical framework for understanding of the nature of energy balance in humans. More recently, alternative approaches have been proposed which take account of how different fuels are partitioned among metabolic pathways. The body responds differently to overfeeding with different nutrients, suggesting that balance equations for separate nutrients might be more informative. Protein balance is achieved on a day-to-day basis, with oxidation of intake in excess of needs; and carbohydrate intake stimulates both glycogen storage and glucose oxidation, with negligible conversion to TAG under dietary conditions of industrialized countries. In marked contrast, fat intake has little inﬂuence on fat oxidation so that energy balance is virtually equivalent to fat balance and there is a strong relationship between fat balance and energy balance even over a period as short as 24 h. Chronic imbalance between fat intake and fat oxidation may therefore predispose to increased fat storage. This line of thinking leads to the conclusion that physical activity has greater potential to inﬂuence body energy stores than would be deduced on the basis of the tradtional energy balance equation. Fat oxidation is of course enhanced during submaximal exercise, and more so in people who are well trained. It is also enhanced for some hours afterwards, even when the postexercise elevation of metabolic rate has disappeared (Calles-Escandon et al. 1996). The response to a fatty meal is changed, with greater postprandial fat oxidation (Tsetsonis et al. 1997). There might be synergistic beneﬁts of increased exercise if, as discussed above, there is an increased appetite for high carbohydrate foods. Conclusion Substantial elevations in mortality are seen in sedentary and unﬁt men and women. With regard to CHD, a biological gradient has been documented convincingly, although its exact pattern remains unclear; high levels of rather vigorous endurance exercise may be necessary for optimal beneﬁt but some studies show that 51 risk decreases steeply at the lower end of the physical activity (or ﬁtness) continuum, reaching an asymptote in the mid-range. 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