The effect of the menstrual cycle and hyperglycaemia on hormonal and metabolic responses during exercise.

PURPOSE: Variations in substrate metabolism have been identified in women during continuous steady-state aerobic exercise performed at the same relative intensity throughout discrete phases of the menstrual cycle, although some evidence exists that this is abolished when carbohydrate is ingested. This investigation examined the effects of a supraphysiologic exogenous glucose infusion protocol, administered during two phases of the menstrual cycle (follicular and luteal) in eumenorrheic women to identify differences between metabolic, hormonal and substrate oxidative responses. METHODS: During the experimental conditions, blood glucose was infused intravenously at rates to "clamp" blood glucose at 10 mM in seven healthy females (age 20 ± 1 y, mass 55.0 ± 4.1 kg, [Formula: see text] 40.0 ± 1.8 ml/kg/min). Following 30 min of seated rest, participants exercised on a cycle ergometer for 90 min at 60% [Formula: see text]. During the rest period and throughout exercise, blood metabolites and hormones were collected at regular intervals, in addition to expired air for the measurement of substrate oxidation. RESULTS: Significant differences between ovarian hormones and menstrual phase were identified, with estrogen significantly higher during the luteal phase compared to the follicular phase (213.28 ± 30.70 pmol/l vs 103.86 ± 13.85 pmol/l; p = 0.016), and for progesterone (14.23 ± 4.88 vs 2.11 ± 0.36 nmol/l; p = 0.042). However, no further significance was identified in any of the hormonal, metabolite or substrate utilisation patterns between phases. CONCLUSION: These data demonstrate that the infusion of a supraphysiological glucose dose curtails any likely metabolic influence employed by the fluctuation of ovarian hormones in eumenorrheic women during moderate exercise.

The ingestion of combined carbohydrates does not alter metabolic responses or performance capacity during soccer-specific exercise in the heat compared to ingestion of a single carbohydrate.

This study was designed to investigate the effect of ingesting a glucose plus fructose solution on the metabolic responses to soccer-specific exercise in the heat and the impact on subsequent exercise capacity. Eleven male soccer players performed a 90 min soccer-specific protocol on three occasions. Either 3 ml · kg(-1) body mass of a solution containing glucose (1 g · min(-1) glucose) (GLU), or glucose (0.66 g · min(-1)) plus fructose (0.33 g · min(-1)) (MIX) or placebo (PLA) was consumed every 15 minutes. Respiratory measures were undertaken at 15-min intervals, blood samples were drawn at rest, half-time and on completion of the protocol, and muscle glycogen concentration was assessed pre- and post-exercise. Following the soccer-specific protocol the Cunningham and Faulkner test was performed. No significant differences in post-exercise muscle glycogen concentration (PLA, 62.99 ± 8.39 mmol · kg wet weight(-1); GLU 68.62 ± 2.70; mmol · kg wet weight(-1) and MIX 76.63 ± 6.92 mmol · kg wet weight(-1)) or exercise capacity (PLA, 73.62 ± 8.61 s; GLU, 77.11 ± 7.17 s; MIX, 83.04 ± 9.65 s) were observed between treatments (P > 0.05). However, total carbohydrate oxidation was significantly increased during MIX compared with PLA (P < 0.05). These results suggest that when ingested in moderate amounts, the type of carbohydrate does not influence metabolism during soccer-specific intermittent exercise or affect performance capacity after exercise in the heat.

Effect of a 2-h hyperglycemic-hyperinsulinemic glucose clamp to promote glucose storage on endurance exercise performance.

Carbohydrate stores within muscle are considered essential as a fuel for prolonged endurance exercise, and regimes for enhancing such stores have proved successful in aiding performance. This study explored the effects of a hyperglycaemic-hyperinsulinemic clamp performed 18 h previously on subsequent prolonged endurance performance in cycling. Seven male subjects, accustomed to prolonged endurance cycling, performed 90 min of cycling at ~65% VO(2max) followed by a 16-km time trial 18 h after a 2-h hyperglycemic-hyperinsulinemic clamp (HCC). Hyperglycemia (10 mM) with insulin infused at 300 mU/m(2)/min over a 2-h period resulted in a total glucose uptake of 275 g (assessed by the area under the curve) of which glucose storage accounted for about 73% (i.e. 198 g). Patterns of substrate oxidation during 90-min exercise at 65% VO(2max) were not altered by HCC. Blood glucose and plasma insulin concentrations were higher during exercise after HCC compared with control (p < 0.05) while plasma NEFA was similar. Exercise performance was improved by 49 s and power output was 10-11% higher during the time trial (p < 0.05) after HCC. These data suggest that carbohydrate loading 18 h previously by means of a 2-h HCC improves cycling performance by 3.3% without any change in pattern of substrate oxidation.

Pregnant women with endemic pemphigus foliaceus (Fogo Selvagem) give birth to disease-free babies.

Endemic pemphigus foliaceus (PF), also known as Fogo Selvagem (FS), is an organ-specific autoimmune disease mediated by autoantibodies. These autoantibodies are disease specific, predominantly restricted to the IgG4 subclass, and pathogenic, as demonstrated by passive transfer studies. In contrast to pemphigus vulgaris, neonatal skin disease does not appear to occur in babies born to mothers with non-endemic PF or FS. In the present study we have examined 19 mother/neonate pairs where the mother had documented FS. Mothers and neonates were examined soon after delivery and tested by immunofluorescent (IF) techniques for FS autoantibodies either in circulation (mothers' sera or babies' cord blood) or bound to the neonatal epidermis. All neonates included in this study were born with normal skin. Twelve biopsies from 17 neonates showed negative direct IF using both FITC-antihuman IgG or monoclonal anti-IgG subclass antibodies. In five biopsies the epidermal ICS of the babies showed weak staining. In 10 of the 19 cord sera tested, FS IgG autoantibodies were undetectable; in nine, these autoantibodies were present in low titers (less than 1:40). The sera of the mothers showed higher titers of FS autoantibodies, and IgG4 was the predominant IgG subclass autoantibodies. It appears that human placenta may modulate the expression of disease in the newborn by operating as a "biologic immunoadsorbent" of pathogenic autoantibodies.

Comparison of the metabolic effects of continuous postoperative enteral feeding and feeding at night only.

The effects of two different feeding patterns on oxygen consumption, nitrogen balance, blood biochemistry, and urinary catecholamine excretion were investigated over 5 d in patients after major head and neck surgery. Both groups of nine patients each were fed a regimen that provided 4.7 MJ on day 1 and 10 MJ on days 2-5 via a nasogastric tube by continuous infusion with an enteral feeding pump. One group was fed continuously for 24 h, the other was fed only at night, ie, from 1700 to 0900 the next morning. Oxygen consumption was significantly higher (P less than 0.01), nitrogen balance better (P less than 0.05), and urinary catecholamine excretion higher (P less than 0.05) in the 24-h-fed patients than in the night-fed patients. Postoperatively, feeding at night only is more energy efficient than is feeding continuously for 24 h, but is associated with poorer nitrogen balance. These differences may be mediated by sympathoadrenal mechanisms.

The measurement of food and energy intake in man-an evaluation of some techniques.

A dietary survey was carried out on an Antarctic base over a period of 6 to 12 months on twelve individuals. Three methods of determining individual food and energy intake were used-weighing and recording of food as eaten in combination with food tables, dietary recall, and bomb calorimetry of duplicate meals. Use of weighed food intakes and food composition tables underestimated energy intake by 7% when compared to analysis of duplicate meals by bomb calorimetry. One week was found to be the most practical period over which intake should be measured to determine "habitual" food intake.

The measurement of daily energy expenditure--an evaluation of some techniques.

An energy balance survey was conducted on an Antarctic base on 12 individuals for periods varying between 6 and 12 months. Energy expenditure was estimated using two activity/dairy card techniques and mean 24-hr heart rate used in conjunction with a variety of derived heart rate/energy expenditure regression equations. The accuracy of the various techniques was determined by comparison with estimates obtained using energy intakes and changes in body fat. No method of measuring energy expenditure was accurate enough to predict fat gain or loss. Errors in individuals were large and random but the mean error in the estimation of energy expenditure of the community was reasonable. When using the dairy card there was no difference between using measured values for energy costs of specific activities and using values taken from the literature. Using heart rate was no less accurate than the diary card if energy expenditure was predicted from a regression line derived from heart rate and log energy expenditure, and the technique was more acceptable to the subjects.

A longitudinal study of body weight and body fat changes in Antarctica.

Body weight and body fat changes (calculated from skinfold thickness) that occurred in a male population spending a year on an Antarctic base are described. There was a marked individual variation in patterns of weight and fat changes between seasons but mean values for the whole community showed little change over the year. Combining skinfold and body weight measurements revealed probable individual differences in fat gain or loss with weight gain and loss, but the role of changes in total body water or fat-free mass could not be determined. The possibility of combining long-term measurements of body fat and energy intake to provide an estimate of energy expenditure is discussed.

Muscle thickness, measured with ultrasound, may be an indicator of lean tissue wasting in multiple organ failure in the presence of edema.

Multiple organ failure (MOF) is accompanied by muscle wasting, but changes in body composition are frequently obscured by fluid retention (edema), mainly in superficial and visceral tissue. There is a need to assess body composition and changes in body composition in these circumstances independently of edema. A relation was sought between fat-free (lean tissue) mass [calculated from body weight and skinfold thicknesses and measured by using dual-energy X-ray absorptiometry (DXA)] and muscle thickness (measured using ultrasound at a variety of sites accessible in an unconscious supine subject) to determine which sites correlated best with lean body mass. The three best sites were midbiceps, midforearm anteriorly, and midthigh anteriorly: R2 for the simple sum of the three sites correlated with fat-free mass from skinfold thicknesses was 71.1%, and with lean tissue mass from DXA was 76.1%. Serial measurements of both muscle thickness and midupper-arm circumference in nine patients with MOF showed a complete dissociation; in all nine there was a significant negative correlation of muscle thickness with time (P < 0.05) but changes in arm circumference were random. Only one patient showed a significant negative correlation with time, seven showed no change, and one other showed a significant increase. The muscle thicknesses that correlate best with lean body mass are measured over the biceps, anterior forearm, and anterior thigh. Monitoring muscle thicknesses at these three sites identifies wasting in edematous patients as it is happening.

A comparison of the effects of intermittent and continuous nasogastric feeding on the oxygen consumption and nitrogen balance of patients after major head and neck surgery.

Ten patients were fed by nasogastric tube for 5 days after major surgery of the head and neck. Five were fed by continuous infusion 24 h/day using an enteral nutrition pump and five were fed comparable quantities by 2-h bolus administration between 0600 and 2200 h. Those fed by bolus had lower resting oxygen consumption on the 4th and 5th postoperative days and better cumulative nitrogen balance over the 5 days than the continuously fed group. It appears that metabolically it may be better to use an intermittent feeding regimen than a continuous one when feeding patients postoperatively via a nasogastric tube.

Hormonal and metabolic responses to maintained hyperglycemia during prolonged exercise.

We studied the effects of maintained hyperglycemia (12 mmol/l) on endurance exercise to determine the hormonal and metabolic responses, the maximal rate of glucose infusion (i.e., utilization), and the effects on muscle glycogen stores. Eight men undertook two trials during which they exercised on a cycle ergometer at an intensity of approximately 70% peak O(2) uptake for 120 min. In the first trial (trial A), subjects had their blood glucose concentration clamped at 12 mmol/l 30 min before exercise and throughout exercise. The same rate and volume of infusion of saline as had occurred for trial A were used in a placebo trial (trial B). Maintained hyperglycemia resulted in significantly lowered plasma concentrations of nonesterified fatty acid, glycerol, 3-hydroxybutyrate, epinephrine, norepinephrine, and growth hormone (P < 0.001) during exercise, whereas concentrations of plasma insulin were significantly elevated (P < 0.001). Calculations of the rates of total carbohydrate oxidation showed that trial A resulted in significantly higher values when compared with trial B (P < 0.01) and that the maximal rates of glucose infusion varied between 1.33 and 2.78 g/min at 100-120 min. Muscle glycogen concentrations were significantly depleted (P < 0.01) after both trials (trial A, 170.3 micromol/g dry wt decrease; trial B, 206 micromol/g dry wt decrease), although this apparent difference may be accounted for by storage of 22.6 g glucose during the 30-min prime infusion. The results from this study confirm that maintained hyperglycemia attenuates the hormonal response and promotes carbohydrate oxidation and utilization and that muscle glycogen may not be spared.

Physiological and metabolic responses to a hill walk.

The physiological and metabolic demands of hill walking have not been studied systematically in the field despite the potentially deleterious physiological consequences of activity sustained over an entire day. On separate occasions, 13 subjects completed a self-paced hill walk over 12 km, consisting of a range of gradients and terrain typical of a mountainous walk. During the hill walk, continuous measurements of rectal (T(re)) and skin (T(sk)) temperatures and of respiratory gas exchange were made to calculate the total energy expenditure. Blood samples, for the analysis of metabolites and hormones, were taken before breakfast and lunch and immediately after the hill walk. During the first 5 km of the walk (100- to 902-m elevation), T(re) increased (36.9 +/- 0.2 to 38.5 +/- 0.4 degrees C) with a subsequent decrease in mean T(sk) from this time point. T(re) decreased by approximately 1.0 degrees C during a 30-min stop for lunch, and it continued to decrease a further 0.5 degrees C after walking recommenced. The total energy intake from both breakfast and lunch [5.6 +/- 0.7 (SE) MJ] was lower than the energy expended [14.5 +/- 0.5 (SE) MJ; P < 0.001] during the 12-km hill walk. Despite the difference in energy intake and expenditure, blood glucose concentration was maintained. The major source of energy was an enhanced fat oxidation, probably from adipose tissue lipolysis reflected in high plasma nonesterified fatty acid concentrations. The major observations were the varying thermoregulatory responses and the negative energy balance incurred during the hill walk. It is concluded that recreational hill walking can constitute a significant metabolic and thermoregulatory strain on participants.

Energy balance, metabolism, hydration, and performance during strenuous hill walking: the effect of age.

We aimed to examine the effect of age on energy balance, metabolism, hydration, and performance during 10 days of strenuous hill walking. Seventeen male subjects were divided into two groups according to their age. The nine subjects in group 1 constituted the younger group (age 24 +/- 3 yr), whereas eight older subjects were in group 2 (age 56 +/- 3 yr). Both groups completed 10 consecutive days of high-intensity hill walking. Mean (range) daily walking distances and ascent were 21 km (10-35 km) and 1,160 m (800-2,540 m), respectively. Energy intake was calculated from weighed food intake, and energy expenditure was measured by the doubly labeled water method. Blood and urine were sampled on alternative days to determine any changes in metabolism and hydration during the 10 days. Subjects also completed a battery of tests that included muscular strength (handgrip), jump performance, cognitive processing time, and flexibility. The younger group remained hydrated, whereas the older group became progressively dehydrated, indicated by a near twofold increase in urine osmolality concentration on day 11. This increased urine osmolality in the older group was highly correlated with impairment in vertical-jump performance (r = -0.86; P < 0.05) and decreased cognitive processing time (r = 0.79; P < 0.05). Despite energy expenditure of approximately 21 MJ/day, body mass was well maintained in both groups. Both groups displayed a marked increase in fat mobilization, reflected in significantly lowered prewalk insulin concentrations and elevated postwalk glycerol and nonesterified fatty acid concentrations. Despite the dehydration and impaired performance in the older group, blood glucose concentrations were well maintained in both groups, probably mediated via the increased mobilization of fat.

Metabolic and appetite responses to prolonged walking under three isoenergetic diets.

The effects of three isoenergetic diets on metabolic and appetite responses to prolonged intermittent walking were investigated. Eight men undertook three 450-min walks at intensities varying between 25-30 and 50-55% of maximal O2 uptake. In a balanced design, the subjects were given breakfast, snacks, and lunch containing total carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body mass): mixed diet, 302 CHO, 50 P, 84 F; high-CHO diet, 438 CHO, 46 P, 35 F; high-fat diet, 63 CHO, 44 P, 196 F. Substrate balance was calculated by indirect calorimetry over the 450-min exercise period. Blood samples were taken before exercise and every 45 min during the exercise period. The high-fat diet resulted in a negative total CHO balance (-140 +/- 1 g) and a lower negative fat balance (-110 +/- 33 g) than the other two diets (P < 0.05). Plasma glucagon, nonesterified fatty acids, glycerol, and 3-hydroxybutyrate were higher with the high-fat diet (P < 0.05 vs. high CHO), whereas plasma insulin was lower after high fat (P < 0.05 vs. mixed and high CHO). Subjective ratings of fatigue and appetite showed no differences between the three trials. Although diet influenced the degree of total CHO and fat oxidation, fat was the main source of energy in all trials.

Metabolic and performance responses during endurance exercise after high-fat and high-carbohydrate meals.

We studied the effects of preexercise meal composition on metabolic and performance-related variables during endurance exercise. Eight well-trained cyclists (maximal oxygen uptake 65.0 to 83.5 ml . kg-1 . min-1) were studied on three occasions after an overnight fast. They were given isoenergetic meals containing carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body wt): high-carbohydrate meal, 215 CHO, 26 P, 3 F; high-fat meal, 50 CHO, 14 P, 80 F. On the third occasion subjects were studied after an overnight fast. Four hours after consumption of the meal, subjects started exercise for 90 min at 70% of their maximal oxygen uptake, followed by a 10-km time trial. The high-carbohydrate meal compared with the high-fat meal resulted in significant decreases (P < 0.05) in blood glucose, plasma nonesterified fatty acids, plasma glycerol, plasma chylomicron-triacylglycerol, and plasma 3-hydroxybutyrate concentrations during exercise. This was accompanied by an increase in plasma insulin (P < 0.01 vs. no meal), plasma epinephrine, and plasma growth hormone concentrations (each P < 0.05 vs. either of the other conditions) during exercise. Despite these large differences in substrate and hormone concentrations in plasma, substrate oxidation during the 90-min exercise period was similar in the three trials, and there were no differences in performance on the time trial. These results suggest that, although the availability of fatty acids and other substrates in plasma can be markedly altered by dietary means, the pattern of substrate oxidation during endurance exercise is remarkably resistant to alteration.

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome.

BACKGROUND: The association between depression and pain, function, medically unexplained symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS: Both CFS groups differed significantly from the primary depression group but not each other in the prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study depended on recall of symptoms, not confirmed by medical records and current investigations. Patients with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may improve social function.

Practical limitations of the Deltatrac indirect calorimeter.

Indirect calorimetry is used to assess energy requirements. The Deltatrac Metabolic Monitor is a relatively inexpensive indirect calorimeter which uses a 'fixed' flow of ambient air to collect expired air. Only oxygen and carbon dioxide concentrations are measured and the 'fixed flow' is assumed in the calculation of oxygen consumption ((.)VO(2)) and carbon dioxide production ((.)VCO(2)). Using inert gas dilution we have studied the effect on (.)VO(2), and on the variability in (.)VO(2), of changing and lengthening the 1.77 m length of 35 mm tubing supplied with the instrument to collect expired air, and of using a mask to collect expired air instead of the manufacturer's hood. One would anticipate that changing the tubing could cause a change in resistance to gas flow and thus affect the true flow rate. This would alter the gas concentrations seen by the analysers, but the 'fixed flow' would still be assumed so the results would be in error. Adding extra lengths of manufacturers tubing caused an apparent rise in (.)VO(2) of 0.36%/m of tubing added, and using 22 mm tubing instead of the manufacturer's 35 mm tubing increased (.)VO(2) by 0.42% for each 10 cm of tubing added. Using the mask to collect expired air instead of the canopy (.)VO(2) was higher, possibly due to the energy cost of holding the mask, and was more variable, probably because of poorer mixing of the expired air. To measure (.)VO(2) using a mask with the same precision as a 10 min measurement made with the hood would entail measuring (.)VO(2) for 14.5 min. The methods used to collect expired air (mask or canopy, length and type of tubing) when measuring metabolic rate with the Deltatrac do affect the results obtained but these effects are small and predictable.

Gastric pressure response to low dose dopamine infusion in normal man.

The gastric pressure response to distension was measured during intravenous infusion of dopamine at a rate of 2 mug min(-1)kg(-1) over 2h 50min in 5 normal volunteers to determine whether dopamine at this dose potentiated gastric adaptive relaxation, leading to a fall in gastric pressure and thus a potential delay in gastric emptying. This would be of obvious importance in patients being given dopamine at this dose to support renal function and at the same time being fed by nasogastric tube. The pressure response decreased during the first hour in all five subjects (p < 0.01). In 2 it recovered during the third hour to pre-infusion values, but in 2 it remained diminished; in 1 subject the results were equivocal. Circulating dopamine, noradrenaline and adrenaline concentrations all increased during dopamine (p < 0.05), but compared with control there was no difference in plasma free fatty acids, glycerol, cortisol or glucose concentrations. Dopamine at 2 mug min(-1) kg(-1) produced a transient fall in gastric pressure in all subjects, and a persistent fall in some. The changes in gastric pressures were seen at infusion rates that produced no metabolic or inotropic effects.

Human erythrocyte and plasma amino acid concentrations during exercise.

PURPOSE: This investigation examined the effects of exercise and maltodextrin (Md) or placebo (Pl) ingestion on plasma and erythrocyte concentrations of amino acids. METHODS: The erythrocyte and plasma concentrations of 17 amino acids, as well as plasma glucose and insulin, were analyzed in eight healthy trained male subjects before, during, and 25 min after 90-min cycle ergometer exercise at 65% peak oxygen uptake. The two treatments involved ingestion of orange-flavored water (Pl) or orange-flavored 10% maltodextrin solution (Md). RESULTS: Two-way ANOVA revealed 1) that plasma concentrations of alanine and tyrosine changed significantly during the treatments, 2) that the plasma concentrations were significantly different between treatments for glycine and threonine, 3) that all erythrocyte concentrations increased significantly throughout the treatments except for arginine and tyrosine, and 4) that there were no significant differences in erythrocyte concentrations between the treatments. Three-way ANOVA highlighted the significant differences in the time responses between plasma and erythrocyte concentrations; the changes in erythrocyte levels from rest being significantly different from plasma for all amino acids except aspartic acid, glycine, and ornithine. Plasma glucose concentrations became elevated and remained above rest values in Md but fell below rest values in Pl: the differences in concentration between treatments were significant. Correspondingly, plasma insulin was significantly higher in Md during exercise. CONCLUSION: These results highlight that far from being slow in the uptake of amino acids, the erythrocyte in fact sequesters amino acids at an appreciable rate during exercise without a corresponding elevation in the plasma amino acids. For a greater understanding of amino acid changes during exercise, the analysis of both plasma and erythrocytes is recommended.

Limitations of nutrient intake. The effect of stressors: trauma, sepsis and multiple organ failure.

The response to injury includes a diminution in appetite, a decrease in nutrient intake, an acute mobilisation of endogenous energy stores (glucose and fat), but an impaired ability to use them. Lean tissue is broken down to its constituent amino acids, which provide precursors for the synthesis of glucose in the liver (gluconeogenesis). Glucose is used as a source of energy by the brain and red blood cells, as well as by wound tissue. After a discrete injury normal function is normally resumed with a reduced body mass. In very severe injury or sepsis, in those who are physiologically or immunologically impaired or those with a genetic predisposition to the condition, organ failure may develop due to an apparent ongoing inflammatory process. The origin of this process is not always apparent, but loss of integrity of the gastrointestinal tract has been suggested. Apparently adequate nutritional support in the presence of a severe inflammatory stimulus only attenuates the gluconeogenic process, and the breakdown of lean tissue continues. Supply of protein (amino acids) stimulates protein synthesis, but it also stimulates breakdown. Nutrient intake via the enteral route may be limited by gastrointestinal symptoms and via the parenteral route by fluid overload, although this can be circumvented by fluid removal by haemofiltration. It is probable that, if nutritional support in severe trauma/sepsis/multiple organ failure is to be effective, satisfactory pharmacological methods of controlling metabolism will have to be found.