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J Clin Pathol: first published as 10.1136/jcp.42.11.1121 on 1 November 1989. Downloaded from J Clin Pathol 1989;42:1121-1 125 Occasional article Chemistry of marathon running A C AMES From the Department ofChemical Pathology, Neath General Hospital, Neath, West Glamorgan Introduction performance to be reached. Intensive training increases the maximal cardiac output and blood The upsurge of interest in the beneficial effects of volume of skeletal muscles, and by conditioning, exercise and participation in endurance events like increases the mitochondrial density, oxidative marathon running, which started in the early 1980's, enzymes, and myoglobin in muscle cells. These adap- has been maintained, and the 22000 competitors who tations combine to raise the maximal total body completed the 1989 London Marathon bear witness to oxygen consumption (V02 max), thus enabling greater the continuing involvement of a mass ofordinary men workloads to be tolerated with a consequent and women. Most who train and compete regularly improvement in endurance.2 undergo adaptive physiological changes, with During aerobic metabolism, intracellular muscle improved physical fitness and benefits to long term glycogen and triglyceride with extracellular glucose health. For a few, rigorous exercise is not without its and free fatty acids (FFA) are oxidised to provide copyright. hazards to health. energy. As glycogen stores become depleted during This review briefly and selectively outlines the prolonged exercise the relative contribution from FFA normal physiological responses, together with adverse increases, and this ability to oxidise FFA at any pathological effects and their clinical consequences intensity of exercise is an important adaptation of where appropriate. training. If tissue oxygenation becomes inadequate, anaerobic glycolysis occurs with the production of General metabolism lactate. During a marathon race, muscle glycogen stores http://jcp.bmj.com/ The ability of a person to become a high performance, become depleted at around 20 miles, fatigue occurs, endurance athlete is inherited and is due primarily to and poorly prepared runners experience a state of the predominance of slow twitch fibres in skeletal exhaustion referred to as "hitting the wall". Whether muscle-unlike sprinters and jumpers who have a this state is experienced depends on the degree of higher proportion of fast twitch fibres. fitness, the intensity of exertion, the degree of hydra- Slow twitch fibres have a low contractile speed, tion and the initial level of muscle glycogen. FFA producing minimal but highly efficient force with low become the major energy source and performance on September 29, 2021 by guest. Protected fatiguability. This is largely due to their low myosin progressively deteriorates. adenosine triphosphatase content and the poor affin- Many factors may contribute to exhaustion and ity of troponin for calcium. They have more fatigue. The untrained athlete is more likely to suffer capillaries, more mitochondria and greater oxidative from ketosis after exercise, and the increased produc- capacity, more myoglobin and less glycogen than fast tion of pyruvate, acetoacetate, and 3-hydroxy- twitch fibres. Slow fibres, therefore, have a greater butyrate can exert an antilipolytic and hypoglycaemic capacity to produce energy for long periods using effect in high concentrations. The concentration of aerobic metabolism, being less efficient under serum lactate is higher in this group in contrast to the anaerobic conditions.' conditioned athlete who shows a minimal increase. Regular aerobic exercise, which involves a proges- This is probably due to enhanced metabolism of sive increase in cardiorespiratory and muscle activity, lactate, either by muscle oxidation or hepatic gluco- induces physiological changes which enable peak neogenesis.3 Hypoglycaemia can occur in endurance events lasting more than four hours and the untrained Accepted for publication 7 June 1989 person is more susceptible,4 but its presence does not 1121 J Clin Pathol: first published as 10.1136/jcp.42.11.1121 on 1 November 1989. Downloaded from 1122 Ames necessarily limit endurance if FFA are readily avail- increase in HDL-C through exercise conditioning able. would help to delay the development of ischaemic To prevent or delay collapse from exhaustion the heart disease and premature coronary thrombosis. amount ofstored muscle glycogen can be increased by Although various studies in several species of dietary manipulation before the race. This is referred animals indicate that the development of athero- to as "carbohydrate loading". It involves depletion of sclerosis is reduced by regular exercise, it remains muscle glycogen before the race by a combination of speculative whether it is beneficial in man in the exercise and a diet high in protein and fat, but low in primary prevention of ischaemic heart disease.' carbohydrate for three days. This is followed by a diet Epidemiological studies have failed to provide con- high in complex carbohydrates, forming 80% of the clusive proof that regular aerobic exercise offers total calorie consumption for a similar period before protection from the morbidity and mortality the event. Glycogenesis is stimulated and glycogen in associated with ischaemic heart disease because ofthe the leg muscles can be doubled compared with that difficulty of long term projects in controlling the obtained on a mixed conventional diet. This man- multiple risk factors involved. Nevertheless, there are oeuvre significantly increases the time exercise can be several reports" covering a variety of sports where a maintained, improving endurance, and delaying the reduced incidence of ischaemic heart disease has been onset of fatigue.5 Carbohydrate loading, which in an observed with improved longevity in athletes who average man involves the storage of700 g ofglycogen, regularly participate. Life expectancy may be requires 2 litres ofwater for intracellular storage which increased by up to three years, but to achieve this it has may, incidentally, delay the effects of dehydration. been estimated that a comparable time would have to Caffeine taken as strong coffee before a race, by be dedicated to exercise! This would involve running stimulating lipolysis and release of FFA, has a orjogging 20 miles a week with an energy expenditure glycogen sparing action and contributes to better of 2000 kilocals on a regular basis, indefinitely. endurance. Sudden death and myocardial infarction Lipoproteins, atherosclerosis, and ischaemic heart disease Sudden death during or while recovering from stren-copyright. uous exercise is rare. Participation during the incuba- Investigations to assess the effect of endurance exer- tion period of a viral illness can aggravate and cause cise on serum lipoproteins have shown variable and death from myocarditis. Most reported cases are due inconsistent results. The weight of evidence indicates to cardiac arrhythmias secondary to underlying that serum triglyceride (TGL), total and low density coronary artery disease. Myocardial ischaemia in the lipoprotein cholesterol (LDL-C) are reduced and that face of an increased oxygen demand predisposes to high density lipoprotein cholesterol (HDL-C) is ventricular fibrillation. The only practical screening increased. Many studies have been inconclusive due to procedure to detect ischaemic heart disease before http://jcp.bmj.com/ the difficulty ofdetermining whether these changes are regular high level exercise is undertaken is electro- directly attributable to exercise, rather than a change cardiography, but the high incidence of abnormal in lifestyle which incorporates healthy eating with a tracings in 10% of well trained but otherwise normal reduced fat intake, reduction in obesity, and abstin- athletes makes interpretation very difficult. ence from tobacco and alcohol.2 Bundle branch block, pseudo-ischaemic T waves, an When compared with sedentary people, endurance increase in ST-segment and postero-inferior ischaemic runners, skiers, and cyclists are able to maintain patterns are not unusual,'0 but the development of significantly lower LDL-C and TGL and higher HDL- coronary thrombosis, which depends on the presence on September 29, 2021 by guest. Protected C serum concentrations. It is also evident that those at ofpre-existing atherosclerosis, is unpredictable. It also risk from premature ischaemic heart disease who have requires the presence of a hypercoagulable state, high TGL, LDL-C and low HDL-C concentrations which may be stimulated by physical stress or exercis- benefit favourably from regular exercise, thereby ing in conditions of extreme heat and humidity. reducing the risk.6 The diagnosis ofmyocardial infarction in a "collap- The mechanisms for the change in serum lipid sed" runner with an abnormal ECG can cause diag- profile remain undetermined. Attention has focused nostic problems. The increased activity in serum on the induction of higher activities of lipolytic "cardiac enzymes" may be difficult to interpret as enzymes such as lipoprotein lipase in muscle and severe exercise results in significant increases of adipose tissue after exercise, but similar changes occur creatine kinase (CK), lactate dehydrogenase, aspar- with weight loss alone, which is also associated with an tate, and alanine aminotransferase activities which are increase in HDL-C. It might be anticipated that a released from skeletal muscle." Increased muscle cell sustained reduction in LDL-C associated with an membrane permeability