Lars Lindmark

Whole-body tyrosine flux in relation to energy expenditure in weight-losing cancer patients

Whole-body tyrosine flux was measured in seven weight-losing cancer patients and compared with that of seven noncancer patients with malnutrition. L[U-14C] tyrosine was infused intravenously (IV) after an overnight fast under resting conditions and flux rates, oxidation, and incorporation into proteins of tyrosine were calculated from plateau values of specific activity of tyrosine in plasma and of labeled expired carbon dioxide. Rates of protein synthesis were calculated from the flux rate of tyrosine after subtracting the proportion oxidized. Simultaneous measurements of whole-body carbon dioxide production and oxygen uptake were also performed in each subject. Cancer patients had elevated whole-body tyrosine flux, protein synthesis, and energy expenditure when expressed in relation to body weight and whole-body potassium while the differences in tyrosine kinetics became of borderline significance when expressed in relation to energy expenditure. Tyrosine incorporation into whole-body proteins corresponded to a synthesis rate of 2.70 +/- 0.17 protein/kg/d in cancer patients and 2.18 +/- 0.17 in control patients (P less than 0.025). The results show that elevated protein synthesis in weight-losing cancer patients may explain not more than one third of the elevated energy expenditure. Therefore, other systems that utilize energy must increase in activity.

Thermogenic effect of food in physically well-trained elderly men

SummaryBasal metabolic rate (BMR) and the thermogenic effect of food (TEF) after a liquid mixed meal of 2092 kJ (500 kcal) were examined in physically well-trained, elderly men in comparison with sedentary weight- and age-matched controls. BMR tended to be higher and TEF was significantly higher in the physically well-trained men than in the controls. No certain differences were found in plasma thyroid hormones or catecholamines. BMR correlated with whole body potassium while TEF did not. The tendency to elevated BMR in the well-trained men might therefore be due to their greater muscle mass. The elevated TEF, however, probably has other causes and might be associated with the elevated catecholamine sensitivity associated with the physically trained condition.

Metabolic alterations in liver, skeletal muscle, and fat tissue in response to different tumor burdens in growing sarcoma-bearing rats

Abstract Metabolic alterations in growing sarcoma-bearing rats were studied and are presented in relationship to a small and moderate tumor burden (5 and 10% dry tumor weight of dry carcass weight). Sarcoma-bearing rats with a small tumor burden had decreased plasma concentration of glucose, significantly changed hepatic protein metabolism, increased lipolysis in fat tissue, but not significantly changed protein metabolism in skeletal muscles. Tumor-bearing rats with a moderate tumor burden had altered hepatic protein metabolism and plasma glucose in a manner similar to rats with a small tumor and similar to that previously reported for nongrowing sarcoma-bearing mice with a large tumor. This was also similar to findings in cancer patients. (K. Lundholm, S. Edstrom, I. Karlberg, L. Ekman, and T. Schersten, Cancer Res. 40 : 2516–2522, 1980; K. Lundholm, S. Edstrom, L. Ekman, I. Karlberg, A-C. Bylund, and T. Schersten, Cancer 42 , 453–461, 1978). In contrast to sarcomabearing mice and man, these rats with a “moderate tumor” still had unchanged nitrogen balance in skeletal muscle. We conclude that metabolic alterations in the liver precede catabolic reactions in peripheral tissues and that initiating factors for increased lipolysis are earlier than those factors initiating wasting of skeletal muscles in growing sarcoma-bearing rats.

Is it Possible to Evaluate the Efficacy of Amino Acid Solutions after Major Surgical Procedures or Accidental Injuries? Evaluation in a Randomized and Prospective Study

Two unbalanced amino acid solutions (essential amino acids, branched-chain amino acids) were compared to a complete and balanced amino acid solution with regard to efficacy of nitrogen balance. Patients were randomized to receive the amino acid solutions over 3 days for each regimen. The patients were examined postoperatively or directly after accidental trauma. Nonprotein calories were given as 40 kcal/kg/day consisting of 50% fat and 50% glucose. Nitrogen was given at the amount of 0.15 g N/kg/day. Unbalanced amino acid solutions gave a 2-fold more negative nitrogen balance than a balanced and complete amino acid solution. However, this difference disappeared and nitrogen balance approached equilibrium irrespective of the amino acid composition of the infused solutions when nitrogen in blood products was accounted for. All patients received a considerable amount of blood products in a comparable but unpredictable way. Blood products corresponded to around 40% of the daily nitrogen intake. Our study demonstrates that it is not possible to test the efficacy of amino acids for nitrogen retention in patients who are in the need of blood-product transfusions. It is likely that amino acids in blood proteins serve as a significant amino acid source that is utilized for resynthesis of body proteins especially in flow-phase patients with high protein breakdown. This fact has not been sufficiently accounted for in the previous literature.

Evaluation of oxidative metabolism in tumour-host livers as a possible cause of energy loss in cachectic sarcoma-bearing mice

Oxygen consumption has been measured in sarcoma-bearing mice, liver cells and tumour tissue. The aim was to determine whether oxidative metabolism in tumour-host livers contributes to the negative energy balance in non-growing animals with a tumour due to insufficient hepatic adaptation of energy consumption. The oxygen uptake in isolated liver cells from freely fed and starved sarcoma-bearing mice showed a 50% decrease (depressed by 322 mumol O2/hr/g) compared to freely fed controls, while starvation of control animals reduced the oxygen uptake in the liver cells by 30-40%. In host tissues other than the liver, total oxygen uptake was depressed by an average 27% (depressed by 50 mumol O2/hr/g) 10-11 days after tumour implantation. In freely fed animals the ratio between oxygen uptake in the tumour-host liver and the host was 0.13 and 0.18 in sarcoma-bearing and control mice respectively. Depression of oxidative metabolism in tumour-host livers was not associated with ultrastructural alterations in the mitochondria or in other cellular organelles studied by electron microscopy. It is concluded that the negative energy balance in a non-growing tumour-bearing host is not explained by deficient adaptation of the hepatic oxidative metabolism, and that depression of activity metabolism in tumour-bearing animals accounts for depression of the metabolic rate in host tissues other than the liver.

Metabolic effects of nutritional support to cancer patients

An adequate understanding of the utilization of administered nitrogen and energy sources as well as the regulation of whole body energy expenditure are important factors for maintaining body weight and body composition. The efficacy and metabolic consequences of adjunct nutritional support to cachectic cancer patients has recently been investigated in a number of studies. This review examines some recent investigations in this area. Depleted cancer patients seem to have a slightly higher resting energy expenditure but a normal metabolic and energetic response to administration of energy substrates. Studies of protein metabolism suggest that depleted cancer patients have a disturbed metabolic response of protein anabolism compared with depleted controls. This could be due to differences in peripheral versus visceral tissues. Adjunct nutritional support plays an important role in restoring the depleted cancer patients although clear correlation to functional parameters is still lacking.