A. Hyltander

Elevated energy expenditure in cancer patients with solid tumours

Cancer patients (n = 106) and non-cancer subjects (n = 96) were classified as weight stable (n = 70) or weight-losing (n = 132). Cancer patients had elevated resting energy expenditure (REE) compared with either weight-losing (23.6 [0.4] vs. 20.5 [0.5] kcal/kg per day, P less than 0.001) or weight-stable controls (22.0 [0.6] vs. 17.9 [0.4], P less than 0.001). Cancer patients had increased fat oxidation irrespective of weight loss (1.24 [0.07] vs. 0.87 [0.04] mg/kg per min; 1.07 [0.04] vs. 0.78 [0.04], P less than 0.001). Elevated energy expenditure was counter-regulated by a decrease in thyroid hormones. Abnormal liver function had no impact on REE in either group. Heart rate was the most powerful factor for prediction of high energy expenditure in both patients and controls. Elevated energy expenditure was related to the increased heart rate in cancer patients in a significantly higher proportion than that in controls. Increased metabolic rate is a significant component behind weight loss in cancer disease, independent of malnutrition and an elevated adrenergic state may be a likely explanation.

Effect on whole-body protein synthesis after institution of intravenous nutrition in cancer and non-cancer patients who lose weight

Cancer and non-cancer patients received total parenteral nutrition (TPN) corresponding to either 120% or 200% non-protein energy resting energy expenditure. Whole-body tyrosine flux and leg exchange of various metabolites were measured in the fasted and fed state. Feeding with the moderate TPN rate did not stimulate whole-body protein synthesis in either group, but the high rate did. Both TPN rates switched an efflux of branched-chain aminoacids from the leg to an uptake in both groups, but this did not apply to tyrosine or phenylalanine. Only the high TPN rate stimulated glucose uptake across the leg in both groups. The leg exchanges of lactate, glycerol and free fatty acids were not significantly influenced by moderate or high TPN rates in either group, although changes in arterial concentrations indicated significant exchanges in compartments other than leg tissues. Thus standard TPN is insufficient to stimulate overall protein synthesis in both malnourished cancer and non-cancer patients, which may explain why previous studies have demonstrated insignificant functional effects with nutritional support to cancer patients.

Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumours

Abstract. The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight‐losing cancer patients. There tore, weight‐losing cancer patients (n= 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg × 2 (β‐adreneceptor blockade); (b) Indomethacin 50 mg × 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg × 3 (pain reliet) or (d) Placebo x 2. A reterence group of healthy well‐nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg × 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast betore and after drug treatment. β‐blockade reduced REE significantly in cancer patients from 1416 ± 95 kcal day‐1 to 1160 ± 63 kcal day‐1 (P <0.02) and from 1472 ± 69 vs. 1398 ± 62 kcal day‐1, (P <0.01) in the well‐nourished reterence individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reterence patients (5%), (P <0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol. Our results support the suggestion that adrenergic factors are the most important mediators behind elevated resting energy expenditure in weight‐losing cancer patients. Such factors were more important than inflammation and cytokine production related to prostaglandin dependent pathways.

The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma

Abstract. This study has evaluated whether long‐term and permanent total parenteral nutrition (TPN) can protect body composition and exercise capacity during iterated courses of chemotherapy (PVB) in men with testicular carcinoma. Thirty‐three men were randomly allocated by means of a computer based algorithm to receive either TPN (at hospital and home) during the entire chemotherapy period or to rely on spontaneous oral intake only. Nutrition status was assessed by measurements of whole body nitrogen (neutron activation), total body potassium, body water, urine creatinine excretion, loco‐regional body nutrition indexes (AMC, TSF) and biochemical plasma concentrations (albumin, thyroid hormones). Whole body respiratory gas exchanges were measured during resting, submaximal and maximal exercise. TPN was prescribed on an individual basis in all study patients to cover 150% of their measured caloric need; nitrogen was given as 0·2 g N kg‐1 day. All individuals were allowed to eat freely throughout the study.

The role of diet components, gastrointestinal factors, and muscle innervation on activation of protein synthesis in skeletal muscles following oral refeeding

The aim of this study was to quantify the effect of oral refeeding on the synthesis of soluble and contractile proteins in skeletal muscles, and to evaluate to what extent diet components (carbohydrate, fat, amino acids), hormones (insulin, IGF-I, GIP), Ca2+ flux, polyamine synthesis, cyclooxygenase activity, and muscle innervation are related to activation of protein synthesis at the translational level following oral refeeding. Adult, weight-stable, non-growing mice (C57B1) were used in starvation/refeeding experiments with oral chow. Growing rats (150 g) were used in parenteral refeeding experiments. Protein synthesis was measured in vivo in mixed muscles (phenylalanine flooding), in phasic EDL muscles (in vitro), and in cultured L-6 muscle cells. Overnight starvation reduced synthesis of soluble proteins by 37 +/- 8% (from 0.242 +/- 0.025 to 0.151 +/- 0.009 microgram-1.mg-1) and contractile proteins by 55 +/- 6% (from 0.148 +/- 0.018 to 0.068 microgram-1.mg-1) (P < 0.01). Soluble proteins with a basic net charge were more sensitive to nutrition compared to neutral and acidic proteins. Somatostatin treatment before refeeding attenuated muscle protein synthesis by 15% (P < 0.02). Mechanical stimulation of the gastrointestinal tract (bulk feeding) did not activate protein synthesis in muscles, while i.v. or i.p. provision of nutrients did. Oral refeeding normalized rates of protein synthesis within 3 h (P < 0.01), independently of intact muscle innervation, Ca2+ flux, polyamine synthesis, and cyclooxygenase activity in the skeletal muscles, while it was dependent on a complete substrate composition of the oral diet. Our results support the hypothesis that amino acids, probably in concerted action with locally produced tissue IGF-I, stimulate protein synthesis in skeletal muscles during refeeding.