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The intestinal metabolism of aspartame (N-L-alpha-aspartyl-L-phenylalanine methyl ester; APM) and its L-phenylalanine methyl ester (PME) decomposition product was evaluated in six young pigs. Equimolar doses (2.5 mmol/kg body weight) of APM, PME, and L-phenylalanine (PHE) administered to the proximal jejunum produced similar increases in portal blood PHE concentrations. Methanol, nondetectable in portal blood after PHE ingestion, increased markedly after administration of either APM or PME. Portal blood aspartate concentrations were unchanged after PME and PHE administration, but increased significantly after APM administration. Increases in portal blood PHE concentrations were significantly greater than were increases in aspartate concentrations following APM administration. Neither APM, PME, nor aspartyl-phenylalanine (AspPhe) were detected in portal or vena caval blood following administration of any test compound. Steady-state perfusion of the small intestine with APM showed a net intraluminal appearance rate of AspPhe at 36% of the disappearance rate of APM. During steady-state PME perfusion, PHE had a significantly greater net appearance rate than during APM perfusion. Methanol appearance rates were slightly, but not significantly, higher during PME than during APM perfusions. The data suggest that (1) APM is hydrolyzed to AspPhe and both APM and PME are hydrolyzed to their constituent amino acids and and methanol prior to entering the portal circulation; (2) AspPhe is an important intraluminal intermediate in aspartame metabolism; and (3) aspartate is rapidly metabolized by the enterocyte.

Pigs infused with preparations of glucose oligosaccharides excrete sizeable quantities of maltose in urine despite the absence of maltose in the infused solution. Maltose infused without other oligosaccharides is well utilized. Our studies examined possible sources of excreted maltose. We first examined whether simultaneous infusion of larger oligosaccharides with maltose inhibits maltose utilization. Four young pigs were infused for four days with 20 g/d of a maltose-free oligosaccharide preparation to which tracer quantities of U-14C-maltose were added. Urinary excretion of maltose-plus-maltotriose increased significantly (P less than .05) from a mean +/- SD baseline value of .01 +/- .01 g/d to an overall four-day mean value of 1.33 +/- 0.47 g/d. However, only 10.7 +/- 0.78% of infused 14C-maltose was excreted, indicating that simultaneous infusion of larger oligosaccharides did not inhibit maltose utilization. The second study examined whether maltotriose present in the oligosaccharide mixture was the source of excreted maltose. Four young pigs were infused for three days with 20 g/d of a special preparation of oligosaccharides containing only trace quantities of maltose and maltotriose. Urinary maltose plus maltotriose excretion increased significantly (P less than .05) from a mean +/- SD baseline value of .01 +/- .01 g/d to 1.65 +/- 0.41 g/d during oligosaccharide infusion. The data suggest that excreted maltose and maltotriose arise from the catabolism of larger oligosaccharides.

The ability of intravenously administered maltose or glucose to supply 12% of the energy requirements of growing miniature pigs was compared. All pigs were fed a stock diet from days 5 to 28 of life, and a central venous catheter was placed at 28 days. For the next 30 days, all pigs were fed orally and intravenously. Positive control pigs were fed the stock diet with infusions of an isotonic balanced electrolyte solution. Negative control and test animals were fed a diet containing cellulose to replace 12% of energy. Negative control animals received the balanced electrolyte solution intravenously, while test animals received either intravenous glucose or maltose at levels providing 12% of energy. Carbohydrate utilization was measured by loss of urinary carbohydrate, as well as by growth and body composition. Chemical analyses of the urine indicated utilization of both maltose and glucose, but maltose was utilized less well (87%) than glucose (greater than 99%). Growth and body composition data also indicate maltose utilization. The data suggest a possible role for maltose infusion as a supplemental energy source.

The ability of fed or fasted 30-day-old pigs to utilize intravenously administered glucose-oligosaccharides (supplied at 20 g/day) was compared in a randomized crossover design. Six pigs were fed a stock diet from days 10 to 30 of life. A central venous catheter was placed on day 30. From days 30 to 39 of life, either a balanced electrolyte solution or a glucose-oligosaccharide solution was infused through the intravenous (i.v.) catheter. On the first i.v. feeding day, all animals were infused with an isotonic, balanced electrolyte solution and were allowed food and water ad libitum per os. On days 2 through 5 of the i.v. period, 3 animals received glucose-oligosaccharides intravenously (20 g/day), with all other needed nutrients, including energy, supplied enterally. On days 6-9 of the i.v. infusion period these animals continued to receive oligosaccharides intravenously, but were denied food. The other three animals were infused with oligosaccharides in the fed or fasting state in the reverse order. Based on urinary carbohydrate excretion, mean (+/- SD) glucose-oligosaccharide utilization was 92% whether the animals were fed or fasted. These results differ from those observed in fasted human subjects.

N-Acyl-methionine derivatives have been proposed as replacements for methionine in supplementing food products low in this amino acid. We studied the effects of N-acetyl-L-methionine, N-acetyl-D-methionine and L-methionine loads (2 mmol/kg body weight) on portal and vena caval plasma amino acid concentrations in young pigs (n = 4). L-Methionine loading significantly increased mean (+/- SD) portal and vena caval plasma methionine concentrations from baseline values of 6.44 +/- 1.03 and 6.63 +/- 0.99 mumol/100 ml, respectively, to mean peak values of 340 +/- 75.0 and 265 +/- 49.8 mumol/100 ml, respectively. N-Acetyl-L-methionine loading increased mean peak portal and vena caval plasma methionine concentrations to 291 +/- 85 and 220 +/- 51.6 mumol/100 ml, respectively. N-Acetyl-L-methionine could not be detected in either portal or vena caval plasma. In contrast, N-acetyl-D-methionine loading produced only a small rise in mean peak portal and vena caval plasma methionine concentrations (13.0 +/- 4.31 and 8.62 +/- 1.71 mumol/100 ml, respectively). Concentrations of N-acetyl-D-methionine increased from baseline values of 0 mumol/100 ml to mean peak values of 251 +/- 32.0 and 234 +/- 72.3 mumol/100 ml, respectively, in portal and vena caval plasma. These data explain the poor utilization of N-acetyl-D-methionine as a methionine source.

Oligosaccharides are potential sources of carbohydrate-derived energy for use in parenteral nutrition regimens. Clinical studies indicate that although some patients utilize infused oligosaccharides well, many patients do not. These results suggest that oligosaccharides might be useful as a parenteral energy source for selected patients. This report describes a method, suitable for use by nursing staff on the ward, to determine oligosaccharide utilization and identify patients utilizing oligosaccharides well. Oligosaccharides excreted in urine are hydrolyzed enzymaticallly to glucose using α-glucosidase and α-amylase, and the glucose released is measured by a test tape method. The results obtained agree well with the acid hydrolysis-spectrophotometric assay for oligosaccharide excretion used in earlier studies. The method readily identified postsurgical patients utilizing infused oligosaccharides poorly in both prospective and retrospective studies. (Journal of Parenteral and Enteral Nutrition 11:124-128,...

Summary: The ability of intravenously administered glucose or glucose oligosaccharides to supply 12% of the energy requirement of the growing miniature pig was determined. All pigs were fed a stock diet from days 5–28 of life, and a central venous catheter was inserted at 28 days. For the next 30 days, all pigs were fed both enterally and parenterally. Positive control pigs were fed the stock diet with infusions of an isotonic balanced electrolyte solution. Negative control and test animals were fed a diet containing cellulose to replace 12% of energy. Negative control animals received the balanced electrolyte solution intravenously, while test animals received either intravenous glucose or glucose oligosaccharides at levels providing 12% of energy. Carbohydrate utilization was measured by urinary loss of carbohydrate, as well as by growth and body composition. Chemical analyses of the urine indicated utilization of both glucose and glucose oligosaccharides. Glucose oligosaccharides were utilized less well (85%) than glucose (≥99%). No statistically significant differences in weight gain were noted between groups, although weight gain in negative control animals and those animals infused with glucose oligosaccharide solutions were lower than those in the other groups. Body fat analyses also indicate that glucose oligosaccharide solutions were less effective than glucose as an energy source. Speculation: Infusion of solutions containing oligosaccharides composed of repeating glucose units linked by a-1,4glucosidic bonds can supply considerably more energy per osmole infused than glucose. If the human infant utilizes intravenously administered oligosaccharides as well as the growing pig, oligosaccharides may be able to partially replace glucose in parenteral feeding regimens.

Extract: Rates of urinary excretion of total hydroxyproline by 38 normal fullsize male infants were determined on 176 occasions. Each urine collection period was 72 hours. When the period of urine collection was begun between the fourth and eighth day of life, mean rate of excretion was 30.6 mg/day (standard deviation 6.9 mg/day). Maximal rates of urinary excretion were observed between 21 and 60 days of age (mean: 48.1 mg/day; standard deviation 9.7 mg/day). Between 121 and 582 days of age, mean rate of excretion had decreased slightly to 43 mg/day. Eleven infants were each studied on at least five occasions between 20 and 120 days of age. Mean rate of urinary excretion of hydroxyproline by each infant was shown to be significantly correlated with rate of gain in length but not with rate of change in weight or surface area. Speculation: During normal infancy it seems probable that a major proportion of the hydroxyproline excreted in the urine is derived from collagen of bone. Rate of excretion probably parallels rate of bone growth. Thus, any disorder that depresses the normal rate of linear growth is likely to result in sharp diminution of urinary excretion of hydroxyproline. Such a biochemical index of growth may be clinically useful.

Four groups each of eight Pitman-Moore miniature pigs were weaned at 3 days of age and then fed for 25 days on formula diets identical except for the type of carbohydrate. The diets contained thin-boiling waxy corn starch or one of three chemical modifications of this starch (phosphated distarch phosphate, distarch phosphate and hydroxypropylated distarch glycerol). No statistically significant treatment-related effects were observed on growth, biochemical values of blood or serum, or carcass or liver composition.

Essential fatty acid deficiency (EFAD) occurs in infants fed fat-free mixtures of glucose and amino acids. Although infusion of lipid emulsion rapidly reverses clinical symptoms, little is known about effects on tissue fatty acids. To study this question, five groups (n = 4/group) of neonatal pigs were studied. Three groups (I, II, and V) were made EFAD by feeding diets without essential fatty acids (EFA) for days 5 to 33 of life. Groups III and IV were fed a control diet. By 33 days, animals fed the deficient diet showed clinical symptoms and biochemical signs of EFAD. On days 33 to 54 of life, group I animals were fed the EFA-deficient diet and infused with lipid emulsion, providing 3.6% of energy as linoleic acid; group II animals were fed the deficient diet and infused with linoleic acid at 7.2% of energy; group V animals were fed the deficient diet with no lipid emulsion; group III and IV animals were fed the EFA-deficient diet and provided EFA intravenously. Infusion of lipid emulsion rapidly reversed clinical symptoms of EFAD and returned plasma phospholipid ω6 fatty acids levels to normal. However, erythrocyte and liver phospholipid ω6 fatty acid content and adipose tissue reserves of ω6 fatty acids normalized more slowly. Three weeks of infusion of linoleic acid at 3.6% of energy and 2 weeks of infusion at 7.2% of energy were required to return erythrocyte phospholipid fatty acids to normal. Liver phospholipid fatty acid composition still showed biochemical evidence of EFAD in animals treated with linoleic acid at 3.6% of energy for 3 wk. Adipose tissue reserves of ω6 fatty acids did not return to normal in animals treated for 3 wk with linoleic acid at 3.6% of energy. Two to 3 wk of treatment with linoleic acid at 7.2% of energy was required to return adipose tissue 6ω fatty acids reserves to normal.

Plasma and urinary amino acid levels were measured in four normal adult subject administered equimolar quantities (0.0605 mmol/kg body wt) of L-methionine, D-methionine and L-methionine-dl-sulfoxide in a randomized crossover design. Plasma total methionine concentrations increased significantly (P less than 0.05) over base line (3.7 +/- 1.2 mumol/dl; mean +/- SD) after loading with each compound. Mean peak plasma methionine levels were 9.8 +/- 1.1, 14.4 +/- 2.3 and 5.2 +/- 1.0 mumol/dl after loading with L-methionine, D-methionine and L-methionine sulfoxide, respectively. D-Methionine accounted for the increased plasma levels seen after D-methionine loading. None of the three compounds affected plasma cystine, cysteine or taurine concentrations. Plasma methionine sulfoxide concentrations were not affected by loading with D- or L-methionine but increased significantly after ingestion of L-methionine sulfoxide. Urinary methionine excretion was 20 times higher after ingestion of D-methionine than after ingestion of L-methionine or L-methionine sulfoxide, with the increase due to D-methionine excretion. Urinary excretion of methionine sulfoxide and its N-acetyl derivatives was not significantly higher after loading with methionine sulfoxide. The data indicate that adult humans do not utilize D-methionine efficiently as a methionine source but probably do utilize L-methionine-dl-sulfoxide.

Two groups each of eight Pitman-Moore miniature pigs were weaned at 3 days of age and then, for 25 days, were allowed unrestricted access to formula diets identical except for the type of carbohydrate. The diets contained 6% of thin-boiling waxy corn starch or acetylated distarch glycerol. At 14 and 21 days of age, the body weight of pigs fed the control starch diet was significantly higher, while at 28 days, the weight of the empty caecum and the water content of the wet carcass and fat-free wet liver were significantly lower and the carcass-fat and liver-protein contents were significantly greater than the corresponding values for pigs fed the diet containing acetylated distarch glycerol as the sole carbohydrate.

Rats and chickens, unlike man, utilize D-methionine efficiently. We have studied urinary excretion of methionine isomers in young miniature pigs, adult rabbits, and adult dogs given D-methionine in an attempt to find an animal model that, like man, utilizes the D-isomer poorly. Six-week-old miniature pigs ingesting a protein-free diet were infused with 8.5% amino acid solutions differing only in methionine isomer content (L- vs DL-) to supply amino acid requirements. Each solution was infused for a 2- or 3-day period in a cross-over design. Plasma methionine levels were significantly higher (p = 0.01) during infusion of the solution providing DL-methionine, with 25% of total plasma methionine present as the D-configuration. However, urinary methionine excretion was similar with both solutions, with D-methionine utilization calculated as greater than 99%. Adult rabbits ingesting DL-methionine (0.14 g/100 g food) showed good utilization of D-methionine, excreting less than 1.3% D-isomer in the urine. Mixed breed dogs given 1.25 g D-methionine in their drinking water excreted less than 0.4% of ingested D-methionine in the urine. These data indicate that the pig, rabbit, and dog utilize D-methionine efficiently, behaving like the rat and chicken rather than man.

Utilization of intravenously administered oligosaccharides was tested in postsurgical patients by infusing them simultaneously with glucose and amino acids. Thirty two patients were infused with one of two parenteral regimens for four-day periods. Twenty-two patients received a nutritional regimen providing 46 g glucose, 32.5 g amino acids, and 45 g oligosaccharides per liter, while the remaining ten patients received the same solution without oligosaccharides. Patients infused with the test solution received an overall four-day mean +/- SD of 106 +/- 24.2 g oligosaccharide per day. The mean overall four-day excretion of total glucose (free plus oligosaccharide bound) was significantly higher (P less than 0.001) in patients infused with oligosaccharides (46.1 +/- 29.0 g/d) than in reference patients (1.19 +/- 1.20 g/d). Of the total carbohydrate excreted in patients receiving oligosaccharides, 11.3 +/- 13.1 g/d were glucose, 14.8 +/- 13.1 g/d were maltose plus maltotriose, and 20.8 +/- 19.3 g/d were oligosaccharides of maltotetraose size or larger. Although overall utilization of infused oligosaccharide for all patients was only 58.5% +/- 23.1%, three of the patients showed unexpectedly good utilization (94.6% +/- 1.24%).

Previous studies evaluated solutions of small oligosaccharides as potential sources of carbohydrate-derived energy for patients fed intravenously. Although results with these solutions were disappointing, the data suggested that very large oligosaccharides were potential sources of intravenous carbohydrate. To test this hypothesis, four young pigs (3.6 +/- 0.2 kg; mean +/- SD) were infused with sterile solutions for a 6-d period. On days 1 and 6, a balanced isotonic electrolyte solution was infused. On days 2-5 a 9% solution of glycogen was infused at a rate providing 17.7 +/- 0.77 g/d. For each study day the remaining portion of the energy, protein, essential fatty acids and micronutrients was supplied enterally. No adverse reactions were noted during glycogen infusion, and the animals continued to grow. Glycogen utilization was 66.4 +/- 4.3%. Of the total carbohydrate excreted, 85.4% was composed of oligosaccharides of maltotetraose size or larger. Free glucose accounted for 3.5% of the total excreted, while maltose plus maltotriose accounted for 11.1%. Plasma concentrations of oligosaccharide-bound glucose increased during glycogen infusion, rising from a base-line value of 11.0 +/- 14 mg/dL to an overall mean value for the 4-d period of 100.3 +/- 31.6 mg/dL.

Fatty acid composition of carcass and liver and proximate analysis of liver were studied in 14–28 day old Pitman-Moore miniature pigs, 26 sow-reared and 30 fed a semisynthetic diet in which the fat was lard. With increasing age, fat of carcass, but not of liver, became significantly more unsaturated. The percentage of palmitic acid (16∶0) and total saturated fatty acids was significantly greater and the percentage of linoleic acid (18∶2) and total unsaturated fatty acids significantly less in carcasses of male than of female pigs. No sex-related differences in proximate or fatty acid composition of the liver were noted. Carcasses of sow-reared pigs contained significantly greater percentages of myristic (14∶0), palmitoleic (16∶1), and linoleic acids and significantly lesser percentages of stearic (18∶0) and oleic (18∶1) acids than did those of pigs fed the semisynthetic diet. Diet-related differences in fatty acid composition of liver closely paralleled those of carcass, although liver contained markedly greater percentages of stearic and arachidonic (20∶4) acids and lesser percentages of palmitoleic and oleic acids than did carcass. Diet-related differences in fatty acid composition of carcass and liver are discussed in relation to the fatty acid composition of dietary fat (sow milk and lard).

Mean peak plasma glutamate concentrations and area under the plasma glutamate concentration-time curve are much lower in adult humans ingesting monosodium L-glutamate (MSG) in formula than in water. The present study investigated the effects of individual meal components on portal and vena caval plasma glutamate concentration in young pigs administered MSG. Portal vein catheters and gastrojejunal tubes were placed in four young male pigs, and the animals were allowed to recover. Each animal was then administered four water solutions providing 500 mg/kg body weight MSG in a Latin square design. One solution provided only MSG; the second provided MSG and 1 g/kg body weight metabolizable carbohydrate (partially hydrolyzed corn starch); the third provided MSG and 1 g/kg body weight nonmetabolizable carbohydrate (beta-cellobiose); and the fourth provided MSG and 0.4 g/kg body weight of an amino acid mixture (Aminosyn, Abbott Laboratories, North Chicago, Ill). Mean peak plasma glutamate concentration and area under the plasma glutamate concentration-time curve were significantly lower (P less than 0.05) in both portal and vena caval blood when MSG was administered with metabolizable carbohydrate than when administered in water. Simultaneous ingestion of MSG with nonmetabolizable carbohydrate (beta-cellobiose) or amino acids had no significant effect on either mean peak portal or vena caval plasma glutamate concentration or area under the plasma glutamate concentration-time curves when compared to values observed when MSG was administered alone. The data suggest that metabolizable carbohydrate is the meal component affecting plasma glutamate concentration.

Prevention of Fe deficiency was studied with eight Pitman-Moore miniature pigs in each of seven groups. From 5 to 33 days of age the animals received identical cereal-milk diets except for Fe content: diet 1, no added Fe (8 ppm); diet 2, ferrous sulfate; diet 3, catalytically reduced Fe; diet 4, electrolytic Fe powder; diet 5, sodium Fe pyrophosphate; diet 6, ferripolyphosphate powder; diet 7, disodium Fe EDTA. Diets 2-7 provided 64 to 69 ppm of supplemental Fe. Body weight and gain in weight of pigs fed diet 1 did not differ significantly from those of pigs fed diets 2-7; however, gain in body weight between 21 and 28 days of the feeding trial was sig nificantly less in pigs fed diets 1 or 5 than in pigs fed diets 2, 6 or 7. Final Hb and hematocrit values were less than initial values in pigs fed diets 1, 3, 4 and 5. The change in Hb, hematocrit and total Hb Fe of pigs fed diets 1, 3 or 5 differed significantly from those of pigs fed diets 2, 6 or 7. The efficiency with which supplemental Fe was incorporated into Hb ranged between 27 and 30% in pigs fed diets 2, 6 or 7, was 21% in pigs fed diet 4 and approximately 10% in pigs fed diets 3 or 5. Pigs fed diet 1 differed from those fed the other diets in the following manner: liver weight was sig nificantly less; weights of spleen, heart and kidney were significantly greater; less of an intraperitoneal injection of Te was retained in Hb and in organs; of the retained Te, significantly less was found in Hb and significantly more in tissues. Fe status as mea sured by Hb and hematocrit appeared to be inversely correlated with Te concentration in liver, spleen, kidney and heart. J. Nutr. 104: 619-628, 1974.