Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation

BACKGROUND & AIMS: Recent reports suggest that weight loss in cachectic cancer patients may be inhibited by supplementation of the n-3 fatty acid eicosapentaenoic acid (20:5n-3; EPA), presumably due to inhibition of lipolysis. The aim of the present double-blind, randomized trial was to assess whether short-term oral EPA ethyl ester (EE) supplementation inhibits lipolysis and lipid oxidation in weight-losing cancer patients and in healthy subjects. METHODS: Seventeen weight-losing, cancer patients of different tumor types, and 16 healthy subjects were randomized to receive EPA-EE (6 g/d) or placebo (oleic acid (OA)-EE; 6 g/d) for seven days. At baseline (day 0) and during supplementation (days 2 and 7) whole-body lipolysis and palmitic acid release were measured in the overnight fasting state using [1, 1, 2, 3, 3-(2)H(5)]glycerol and [1-(13)C]palmitic acid. Palmitate oxidation was determined by measuring(13)CO(2)enrichment in expired breath. RESULTS: No significant effects of EPA-EE on whole-body lipolysis, palmitic acid release, or palmitate oxidation were detected in cancer patients nor in healthy subjects in comparison with OA-EE. EPA-EE supplementation reduced plasma-free fatty acid and triacylglycerol concentrations significantly in healthy subjects but not in cancer patients. CONCLUSION: We conclude that supplementation of EPA-EE does not significantly inhibit lipolysis or lipid oxidation in weight-losing cancer patients or in healthy subjects during short-term supplementation when using OA-EE as a placebo supplement.     

Effect of two amino acid solutions on leucine turnover in preterm infants

OBJECTIVE: To assess the effect of two different parenteral amino acid mixtures, Trophamine and Primene, on leucine turnover in preterm infants. METHOD: Leucine kinetics were measured with [5,5,5 D3]leucine tracer in 15 infants receiving Trophamine (group 'T') (mean birth weight 1,263 g) and 22 who received Primene (group 'P') (mean birth weight 1,336 g) during two study periods, within a few hours after birth but before introduction of parenteral amino acid solution, and again at postnatal day 7. The rate of appearance of leucine was calculated from the enrichment of alpha-ketoisocaproic acid in plasma. RESULTS: There were no significant differences in leucine turnover within a few hours after birth in the two groups. In the infants who received Primene leucine turnover on day 7 was significantly lower than in those who received Trophamine (269 +/- 43 vs. 335 +/- 27, p < 0.05). Despite a higher intake of leucine in the Trophamine group (108 +/- 10 vs. 77 +/- 8 micromol.kg(-1).h(-1)), leucine released from proteins at day 7 was higher in this group compared to Primene (227 +/- 27 vs. 192 +/- 42 micromol.kg(-1).h(-1)). CONCLUSIONS: Primene administration results in lower leucine released from proteins, an estimate of protein breakdown, than Trophamine in preterm infants. Increases in whole body leucine turnover in response to administration of i.v. amino acids is influenced by the composition of the amino acid mixture. The factors responsible for this difference remain to be elucidated.     

Effect of minimal enteral feeding on splanchnic uptake of leucine in the postabsorptive state in preterm infants

We conducted a controlled, randomized trial to study the effect of minimal enteral feeding on leucine uptake by splanchnic tissues, as an indicator of maturation of these tissues, in preterm infants in the first week of life. Within a few hours after birth, while receiving only glucose, a primed constant infusion of [1-(13)C]-leucine was started and continued for 5 h via the nasogastric tube, whereas 5,5,5 D3-leucine was infused intravenously (for both tracers, priming dose 2 mg/kg, continuous infusion 2 mg/kg/h). Patients were thereafter randomized to receive solely parenteral nutrition (C), parenteral nutrition and 20 mL breast milk/kg/d (BM), or parenteral nutrition and 20 mL formula/kg/d (F). On d 7, the measurements were repeated, after discontinuing the oral intake for 5 h. Fourteen infants were included in group C, 12 in group BM, and 12 in group F. There was no difference in energy intake or nitrogen balance at any time. On d 1, plasma enrichment for the nasogastric tracer was lower than for the intravenous tracer for all three groups, both for leucine and for alpha-keto-isocaproic acid. On d 7, the enrichment for leucine and alpha-keto-isocaproic acid for the nasogastric tracer was lower than for the intravenous tracer for the groups BM and F (BM: 3.65 +/- 1.20 nasogastric versus 4.64 +/- 0.64 i.v.; F: 4.37 +/- 1.14 nasogastric versus 5.21 +/- 0.9 i.v.). In the control group, there was no difference between tracers. The lower plasma enrichment for the nasogastric tracer compared with the intravenous tracer suggests uptake of leucine by the splanchnic tissues. We conclude that minimal enteral feeding--even in low volumes of 20 mL/kg/d--increases the leucine uptake by the splanchnic tissue. We speculate that this reflects a higher protein synthesis of splanchnic tissues in the groups receiving enteral nutrition.     

Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome

OBJECTIVE: Treatment of preterm infants with respiratory distress syndrome (RDS) with exogenous surfactant has greatly improved clinical outcome. Some infants require multiple doses, and it has not been studied whether these large amounts of exogenous surfactant disturb endogenous surfactant metabolism in humans. We studied endogenous surfactant metabolism in relation to different amounts of exogenous surfactant, administered as rescue therapy for RDS. DESIGN: Prospective clinical study. SETTING: Neonatal intensive care unit in a university hospital. PATIENTS: A total of 27 preterm infants intubated and mechanically ventilated for respiratory insufficiency. INTERVENTIONS: Infants received a 24-hr infusion with the stable isotope [U-13C]glucose starting 5.3 +/- 0.5 hrs after birth. The 13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Infants received either zero (n = 5), one (n = 4), two (n = 15), or three (n = 3) doses of Survanta (100 mg/kg) when clinically indicated. MEASUREMENTS AND MAIN RESULTS: Using multiple regression analysis, the absolute synthesis rate (ASR) of surfactant PC from plasma glucose increased with 1.3 +/- 0.4 mg/kg/day per dose of Survanta (p = .007) (mean +/- SEM). The ASR of surfactant PC from glucose was increased by prenatal corticosteroid treatment with 1.3 +/- 0.4 mg/kg/day per dose corticosteroid (p = .004), and by the presence of a patent ductus arteriosus with 2.1 +/- 0.7 mg/ kg/day (p = .01). CONCLUSION: These data are reassuring and show for the first time in preterm infants that multiple doses of exogenous surfactant for RDS are tolerated well by the developing lung and stimulate endogenous surfactant synthesis.     

Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life

BACKGROUND: We recently showed that parenteral administration of amino acids to premature infants immediately after birth is safe and results in a positive nitrogen balance and increased whole-body protein synthesis. However, we did not determine organ-specific effects; albumin, produced by the liver, is an important protein, but its concentration is often low in premature neonates during the first few days after birth. OBJECTIVE: The objective of the study was to test the hypothesis that the fractional and absolute albumin synthesis rates would increase with the administration of amino acids after birth, even at low nonprotein energy intake. DESIGN: Premature infants (<1500 g birth weight), who were on ventilation, received from birth onward either glucose only (control group, n = 7) or glucose and 2.4 g amino acid kg(-1) d(-1) (intervention group, n = 8). On postnatal day 2, all infants received a primed continuous infusion of [1-(13)C]leucine, and mass spectrometry techniques were used to determine the incorporation of the leucine into albumin. Results are expressed as medians and 25th and 75th percentiles. RESULTS: Albumin fractional synthesis rates in the intervention group were significantly higher than those in the control group [22.9% (17.6-28.0%)/d and 12.6% (11.0-19.4%)/d, respectively; P = 0.029]. Likewise, the albumin absolute synthesis rates in the intervention group were significantly higher than those in the control group [228 (187-289) mg kg(-1) d(-1) and 168 (118-203) mg kg(-1) d(-1), respectively; P = 0.030]. CONCLUSION: Amino acid administration increases albumin synthesis rates in premature neonates even at a low energy intake.     

The gut takes nearly all: threonine kinetics in infants

BACKGROUND: Threonine is an essential amino acid that is abundantly present in intestinally produced glycoproteins. Animal studies show that intestinal first-pass threonine metabolism is high, particularly during a restricted enteral protein intake. OBJECTIVE: The objective of the study was to quantify intestinal first-pass threonine metabolism in preterm infants during full enteral feeding and during restricted enteral intake. DESIGN: Eight preterm infants (x +/- SD birth weight: 1.1 +/- 0.1 kg; gestational age: 29 +/- 2 wk) were studied during 2 periods. During period A, 40% of total intake was administered enterally and 60% was administered parenterally. Total threonine intake was 58 +/- 6 micromol kg(-1) h(-1). During period B, the infants received full enteral feeding, and the total threonine intake was 63 +/- 6 micromol kg(-1) h(-1). Dual stable-isotope tracer techniques were used to assess splanchnic and whole-body threonine kinetics. RESULTS: The fractional first-pass threonine uptake by the intestine was remarkably high in both periods: 82 +/- 6% during partial enteral feeding and 70 +/- 6% during full enteral feeding. Net threonine retention was not affected by the route of feeding. CONCLUSION: In preterm infants, the splanchnic tissues extract a very large amount of the dietary threonine intake, which indicates a high obligatory visceral need for threonine, presumably for the purposes of synthesis.     

Comparison of two preterm formulas with or without addition of medium-chain triglycerides (MCTs). I: Effects on nitrogen and fat balance and body composition changes.

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on nitrogen and fat balances and macronutrient oxidation were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There were no differences in nitrogen absorption or in excretion. Median nitrogen retention was 74% (MCT) vs. 71% (LCT) of intake. Fat absorption was higher (p less than 0.05) in the MCT group (88%) vs. 79% in the LCT group (median values). MCTs did not stimulate fat oxidation as measured by indirect calorimetry, so fat deposition was also higher on the MCT formula. As weight gain was not different between groups, the percentage of weight gain consisting of fat accretion was significantly (p less than 0.005) higher with the MCT formula (24% vs. 21%). On the other hand, there was no increase in percent protein accretion (both 15% of weight gain). We conclude that the existence of a slightly lower fat absorption in the healthy growing neonate fed a LCT formula compared with a MCT formula does not impair growth or nitrogen retention, but merely induces a slight decrease in the high relative fat accretion encountered in the preterm neonate.     

Splanchnic oxidation is the major metabolic fate of dietary glutamate in enterally fed preterm infants

The intestine is a major site of amino acid metabolism, especially in neonates. The energy needed for the metabolic processes in neonatal animals is derived from dietary glucose and amino acids. No data are available showing that dietary amino acids function as intestinal fuel source in human neonates as well. We hypothesized that preterm infants show a high splanchnic first-pass glutamate metabolism and the primary metabolic fate of glutamate is oxidation. Five preterm infants (birth weight 1.2+/-0.2 kg, gestational age 29+/-1 wk) were studied by dual tracer ([U-(13)C]glutamate and [D3]glutamate) techniques on two study days (within postnatal d 14-19). Splanchnic and whole-body glutamate kinetics were assessed by plasma isotopic enrichment of [U-(13)C]glutamate and [D3]glutamate and breath CO2 enrichment. Fractional first-pass glutamate uptake was 77+/-18% on d 1, and 70+/-7% on d 2, mean 74+/-13%. Almost all (86+/-7%) of the glutamate used in the first pass is directed toward oxidation. There is a high splanchnic fractional first-pass uptake and a high oxidation rate of glutamate in preterm infants. Glutamate is an important source of energy for the splanchnic tissues in preterm infants receiving full enteral feeding.     

Antiinflammatory effect of mace, aril of Myristica fragrans Houtt., and its active principles

Mace which is the aril of the fruit of Myristica fragrans HOUTT, has been used in Indonesian folk medicine as aromatic stomachics, analgesics, a medicine for rheumatism, etc. The present study was carried out to elucidate the antiinflammatory effect of methanol extract obtained from Mace and its active principles. The methanol extract was extracted with ether, and then the ether soluble fraction was extracted with n-hexane. The n-hexane soluble fraction was fractionated by silica gel column chromatography (Fr-l-Fr-V), and the active principle was isolated from Fr-II by thin layer chromatography (Fr-VI-Fr-VII). The antiinflammatory activity of these fractions was investigated on carrageenin-induced edema in rats and acetic acid-induced vascular permeability in mice. All fractions and indomethacin were suspended in 2% C.M.C. solution and administered p.o. The methanol extract (1.5 g/kg), ether fraction (0.9 g/kg), n-hexane fraction (0.5 g/kg), Fr-II (0.19 g/kg) and Fr-VI (0.17 g/kg) showed a lasting antiinflammatory activity, and the potencies of these fractions were approximately the same as that of indomethacin (10 mg/kg). Fr-VI was determined to be myristicin. These results suggest that the antiinflammatory action of Mace is due to the myristicin that it contains.