This review provides the reader with the up‐to‐date evidence‐based basis for prescribing exercise as medicine in the treatment of 26 different diseases: psychiatric diseases (depression, anxiety, stress, schizophrenia); neurological diseases (dementia, Parkinson's disease, multiple sclerosis); metabolic diseases (obesity, hyperlipidemia, metabolic syndrome, polycystic ovarian syndrome, type 2 diabetes, type 1 diabetes); cardiovascular diseases (hypertension, coronary heart disease, heart failure, cerebral apoplexy, and claudication intermittent); pulmonary diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis); musculo‐skeletal disorders (osteoarthritis, osteoporosis, back pain, rheumatoid arthritis); and cancer. The effect of exercise therapy on disease pathogenesis and symptoms are given and the possible mechanisms of action are discussed. We have interpreted the scientific literature and for each disease, we provide the reader with our best advice regarding the optimal type and dose for prescription of exercise.

SUMMARY1. Five subjects exercised with the knee extensor of one limb at work loads ranging from 10 to 60 W. Measurements of pulmonary oxygen uptake, heart rate, leg blood flow, blood pressure and femoral arterial-venous differences for oxygen and lactate were made between 5 and 10 min of the exercise.2. Flow in the femoral vein was measured using constant infusion of saline near 0 'C. Since a cuff was inflated just below the knee during the measurements and because the hamstrings were inactive, the measured flow represented primarily the perfusion of the knee extensors.3. Blood flow increased linearly with work load right up to an average value of 57 1 min-. Mean arterial pressure was unchanged up to a work load of 30 W, but increased thereafter from 100 to 130 mmHg. The femoral arterial-venous oxygen difference at maximum work averaged 14-6 % (v/v), resulting in an oxygen uptake of 0-80 1 min-. With a mean estimated weight of the knee extensors of 2-30 kg the perfusion of maximally exercising skeletal muscle of man is thus in the order of 2-5 1 kg-' min', and the oxygen uptake 0-35 1 kg-' min-. 4. Limitations in the methods used previously to determine flow and/or the characteristics ofthe exercise model used may explain why earlier studies in man have failed to demonstrate the high perfusion of muscle reported here.5. It is concluded that muscle blood flow is closely related to the oxygen demand of the exercising muscles. The hyperaemia at low work intensities is due to vasodilatation, and an elevated mean arterial blood pressure only contributes to the linear increase in flow at high work rates. The magnitude of perfusion observed during intense exercise indicates that the vascular bed of skeletal muscle is not a limiting factor for oxygen transport.

h z G b T R i j n i , J., L. HERMAXSEK;, E. HULTMAN a n d B. &\LrIN. Diet, mus& ghcogeii a i d p l y i c a l perJi,rmance. Xcta physiol. scand. 1967. 71. 1-10---150. 'l'hc m i i s c l r glycogen content of the quadriccps fcnioris m u s c l e was tlrtcrniincd in 9 I l t d i l i y 5111)jects \\ith the aid of t h r needlr biopsy technique. T h e glycogcn contvnt could br varird in th,.individual subjects by instituting diffcrcrit dicts after rxhatistion of the glycogen stow I>>-hartl cxrrcisc. Thus. the gl>-cogen contcnt aftcr a fat 1 protein ( P ) and a carbohydrate-rich C:J c1iC.t varird maximally from 0.6 g 100 g musclc to 4.7 g . I n all suhjrcts. t h r glycogen content aftcr tlic Cl diet Tvas higher than thr normal range for mriscle glycogen. drtermincd aftcr the mixed ~ 11) dict..iftrr each dirt prrincl. t h r subjects \vorked on a bicycle crgomctcr at a \vork load cirrrspondinq t o 71, pi'r cent of their maximal O L uptake. to complete exhaustion. 'l'he avcragr ivork time \va> -19. 126 and 189 min after diets P, .\I and C:; and a good correlation was noted bct\vren \\t,rk tinit. and rhr initial musclc glycogen content. T h e total carbohydrate utiliation during thr n~~r k prriotls 798 g : was well correlated to the decrease in glycogen contrnt. I t is thrrefbrr coricltidcd that thr g1)cogt:n content of the \\orking musclc is a determinant for thr capacity to prrforni Icinq-[crm heavy cxercisc. hlorru\-rr. it has Iwrn shoivn that thr glycogen content and, conseqrirntl long-trrni w o r k capacity can be appreciably varied by inskitlttinS diEcrrnt diets aftrr $1) dcijl c,tio 11. i 4

Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases, including diseases that do not primarily manifest as disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise therapy in the treatment of metabolic syndrome‐related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and the principles for prescribing exercise therapy are discussed, focusing on the type and amount of exercise and possible contraindications.

Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co‐activator 1α (PGC‐1α) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC‐1α transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one‐legged knee extensor exercise training. At the end of training, subjects completed 3 h of two‐legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3‐hydroxyacyl‐CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P < 0.05) in PGC‐1α transcription (10‐ to > 40‐fold) and mRNA content (7‐ to 10‐fold), peaking within 2 h after exercise. Activation of PGC‐1α was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF‐1) mRNA, a gene induced by PGC‐1α in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor α, and calcineurin Aα and Aβ mRNA were elevated (≈2‐ to 6‐fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC‐1α transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC‐1α may coordinate the activation of metabolic genes in human muscle in response to exercise.

Plasma interleukin (IL)‐6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL‐ The question addressed in the present study was whether the IL‐6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL‐6 accumulating in the blood. This was studied in six healthy males, who performed one‐legged dynamic knee extensor exercise for 5 h at 25 W, which represented 40% of peak power output (Wmax). Arterial‐femoral venous (a‐fv) differences over the exercising and the resting leg were obtained before and every hour during the exercise. Leg blood flow was measured in parallel by the ultrasound Doppler technique. IL‐6 was measured by enzyme‐linked immunosorbent assay (ELISA). Arterial plasma concentrations for IL‐6 increased 19‐fold compared to rest. The a‐fv difference for IL‐6 over the exercising leg followed the same pattern as did the net IL‐6 release. Over the resting leg, there was no significant a‐fv difference or net IL‐6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL‐6 production was 6.8 ng min−1 (kg active muscle)−1 (range, 3.96‐9.69 ng min−1 kg−1). The net IL‐6 release from the muscle over the last 2 h of exercise was 17‐fold higher than the elevation in arterial IL‐6 concentration and at 5 h of exercise the net release during 1 min was half of the IL‐6 content in the plasma. This indicates a very high turnover of IL‐6 during muscular exercise. We suggest that IL‐6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise.

The sections in this article are: Motor Unit Fibers per Motor Unit Contractile Properties Biochemical Basis for Differences in Twitch Properties Histochemical Differentiation of Muscle Fibers Ultrastructural Basis for Skeletal Muscle Fiber Typing Maximal Contractile Force Speed of Contraction Fatigue Characteristics Metabolic Characteristics Ionic Composition of Skeletal Muscle Summary Muscle Fiber Composition in Human Skeletal Muscle Motor‐Unit Recruitment Adaptive Response in Skeletal Muscle Muscle Size Metabolic Capacity Connective Tissue Capillaries Methodology Anatomy Capillary Density Capillary Length and Diameter Use and Disuse Regulation Significance of Adaptation Muscular Size Substrate Stores Enzyme Activities Summary

SUMMARY1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60 % of maximum oxygen consumption rate (VO ) for 9-12 consecutive days at an ambient temperature of 40°C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 0C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40°C on the first and last day.2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating.3. Cardiac output increased significantly from the first to the final heat exposure from 19 6 to 21V4 1 min-1; this was possibly due to an increased plasma volumne and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone.5. The exhaustion coincided with, or was elicited when, core temperature reached 39-7 + 0 15°C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances.6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.