Biomedical subjects
Publications and source records attributed to L J Filer.
In 1970, the National Academy of Sciences reviewed the safety and suitability of modified food starch for use in baby foods. Their report concluded that modified food starches were safe and appropriate for use. A second review, in 1978, by the Committee on Nutrition of the American Academy of Pediatrics, reaffirmed this conclusion. This update provides new information on modified starch utilization and reaffirms its value for use in baby foods.
We tested the hypothesis that ingestion of monosodium L-glutamate with aspartame produces a marked increase in plasma glutamate and aspartate concentrations. Twelve normal adults (6 males, 6 females) ingested three different soup/beverage meals in a balanced Latin square design. One meal (A) provided no aspartame (APM) or monosodium L-glutamate (MSG); a second (B) provided 50 mg MSG/kg body weight; while the third (C) provided 50 mg MSG and 34 mg APM per kg body weight. Plasma glutamate (Glu) concentrations were not significantly affected by meal A but increased significantly after meals B and C (no significant difference between B and C). Plasma aspartate (Asp) concentrations were not significantly affected by meal A but increased significantly after meals B and C (values significantly higher after meal C than meal B). Plasma Glu + Asp concentrations were not significantly affected by meal A but increased significantly from a mean (+/- SD) baseline value of 5.64 +/- 2.62 mumol/dL to high mean values of 23.1 +/- 7.29 and 26.8 +/- 9.74 mumol/dL after ingestion of meals B and C, respectively (no significant difference between meals B and C). Similarly, the area under the plasma Glu + Asp concentration-time curve did not differ significantly between meals B and C (624 +/- 197 v 763 +/- 277 mumol/dL x min, respectively). Peak plasma Glu + Asp concentrations for each subject (ignoring time) were also examined. The mean peak plasma Glu + Asp concentrations were 7.39 +/- 2.77, 23.0 +/- 6.61, and 27.3 +/- 9.07 mumol/dL, respectively after meals A, B, and C.
Some clinical studies require administration of test compounds in capsules to assure that the compound cannot be distinguished from a placebo. This raises the question of whether the pharmacokinetic responses produced by capsule administration are similar to values obtained when test compounds are ingested in solution. To test this, plasma phenylalanine and aspartate concentrations were compared in ten normal subjects ingesting 3 g aspartame in solution and in capsules in a balanced Latin square design. Peak plasma phenylalanine levels were significantly higher (191 +/- 65.4 v 117 +/- 39.5 mumol/L, mean +/- SD) and were reached significantly earlier (32 +/- 15 v 123 +/- 74 minutes) when aspartame was administered in solution than when it was administered in capsules. The area under the four-hour plasma phenylalanine concentration-time curve was significantly higher (15,340 +/- 4,820 v 8,465 +/- 3,356 mumol/L X min) when aspartame was ingested in solution. Administration in solution also produced a significantly higher ratio of plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids (0.36 +/- 0.12 v 0.23 +/- 0.06). Similarly, peak plasma aspartate concentrations were significantly higher 26.2 +/- 16.3 v 10.4 +/- 5.0 mumol/L) and were reached significantly earlier (30 +/- 14 v 106 +/- 61.3 min) when aspartame was administered in solution. The data indicate different plasma phenylalanine and aspartate pharmacokinetics between solution and capsule administration of aspartame.
Twelve normal subjects ingested either unsweetened beverage (n = 6) or beverage providing 4 mg/kg body weight as aspartame (APM) (n = 6). Neither beverage had any significant effect on plasma aspartate or phenylalanine concentrations. After this study, eight normal and six obligate phenylketonuric (PKU) heterozygous adults each ingested a 354-mL (12-oz) beverage serving on two occasions in a randomized cross-over design. On one occasion the beverage was not sweetened; on the other occasion, the beverage provided 10 mg APM/kg body weight. Plasma amino acid concentrations were measured throughout the 2-h study period. The addition of 10 mg APM/kg body weight to the beverage had no significant effect on plasma aspartate concentration. APM ingestion increased plasma phenylalanine levels of normal subjects from a mean +/- SD baseline value of 5.09 +/- 0.82 mumol/dL to a high mean value of 6.73 +/- 0.75 mumol/dL. In PKU heterozygous subjects the plasma phenylalanine level increased from a mean +/- SD of 9.04 +/- 1.71 to a high mean value of 12.1 +/- 2.08 mumol/dL. The data indicate ready metabolism of the aspartate and phenylalanine portion of APM when administered at levels likely to be ingested by individuals who drink diet beverages.
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.
Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate (MSG) is ingested in consomme with starch than when ingested in consomme alone. This study investigated whether sucrose had a similar effect. Six normal adult subjects (three male, three female) ingested two servings of beef consomme each providing 50 mg MSG/kg body weight in a randomized crossover design. One serving of consomme contained no added carbohydrate; the other provided 0.5 g sucrose/kg body weight. Ingestion of the consomme without sucrose significantly (p less than 0.05) increased the mean plasma glutamate concentration from baseline (4.44 +/- 0.97 mumol/dl) to a peak value of 18.1 +/- 6.99 mumol/dl 30 min after dosing. The area under the plasma glutamate concentration-time curve was 553 +/- 238 mumol/dl X min. When the consomme contained 0.5 g sucrose/kg body weight, both the mean peak plasma glutamate concentration (5.48 +/- 2.19 mumol/dl) and the area under the curve (105 +/- 46 mumol/dl X min) were significantly lower. These data confirm that metabolizable carbohydrate has a significant effect on plasma glutamate concentration response after MSG loading.
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.
This study tested the hypothesis that infants metabolize glutamate more slowly than adults. Eight 1-yr-old infants ingested 160 ml of a beef consommé providing monosodium L-glutamate at 0, 25, and 50 mg/kg body weight. Plasma glutamate and aspartate concentrations were measured sequentially for the next 2 h. The results were compared to values noted in nine adult subjects ingesting equivalent doses of monosodium L-glutamate in consommé. In adults, mean (+/- SD) peak plasma glutamate concentrations were 5.59 +/- 1.56, 10.2 +/- 2.08, and 17.0 +/- 8.06 mumol/dl, respectively; the area under the plasma glutamate concentration time curves were 96 +/- 42, 257 +/- 80, and 442 +/- 303 mumol/dl X min, respectively. In infants, the mean (+/- SD) peak plasma glutamate concentrations were 6.94 +/- 1.43, 10.6 +/- 2.36, and 12.0 +/- 1.16 mumol/dl, respectively; the plasma glutamate area under the curve values were 47 +/- 28, 191 +/- 85, and 358 +/- 105 mumol/dl X min, respectively. The data indicate that the plasma glutamate concentration response in 1-yr-old infants ingesting MSG at these glutamate doses is no higher than values observed in adult subjects.
The effect of MSG ingestion in consomme on the plasma glutamate concentration response was studied in normal adult subjects. In the first study nine subjects ingested three different consomme servings (providing 0, 25 and 50 mg/kg body weight MSG) in a Latin square design. Plasma glutamate concentrations were not significantly increased over baseline (3.69 +/- 1.08 mumol/dl) when no added MSG was present. However, mean peak plasma glutamate levels increased proportional to dose when MSG was added (10.2 +/- 2.00 and 17.0 +/- 8.06 mumol/dl at 25 and 50 mg/kg body weight respectively). Since six of the nine subjects in this study reported an idiosyncratic symptom response when tested with MSG at 150 mg/kg body weight, nine additional subjects were also studied. They ingested consomme providing MSG at 0 and 50 mg/kg body weight. No significant differences in plasma amino acid responses were noted between the two groups of subjects.
Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate is ingested in a water solution containing partially hydrolyzed starch than when ingested in water alone. This study was carried out to investigate whether starch ingested as crackers had a similar effect. Eight normal adult subjects (four male, four female) ingested three servings of a beef consommé providing 50 mg/kg body weight monosodium L-glutamate. One serving was consommé alone, the other two were accompanied by sufficient crackers to provide 0.25 or 0.5 g starch per kilogram body weight, respectively. Ingestion of consommé containing glutamate significantly increased the mean plasma glutamate concentration above baseline to a mean peak value 30 min later. The peak after consumption of 0.5 g starch per kilogram body weight, but not 0.25 g/kg body weight, was significantly lower than when consommé alone was ingested. These data indicate that simultaneous ingestion of metabolizable carbohydrate with glutamate has a marked effect on the plasma glutamate response and indicate that the threshold value for carbohydrate is greater than 0.25 g/kg body weight.
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.
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.
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 omega 6 fatty acids levels to normal. However, erythrocyte and liver phospholipid omega 6 fatty acid content and adipose tissue reserves of omega 6 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma, erythrocyte, and urinary amino acid concentrations were measured in young infants infused with a solution containing glutamate and aspartate. Eight infants (1.2 to 2.8 kg) were fed parenterally (80 kcal/kg/day) with two regimens containing dextrose (15 g/kg/day), amino acids (2 g/kg/day), and lipid (2 g/kg/day) for successive 3-day periods in a cross-over design. The regimens differed only in the amino acid source. One regimen (I) provided glutamate (1.5 mmol/kg/day) and aspartate (1.0 mmol/kg/day), while the other regimen (II) did not. The mean (+/- SD) plasma glutamate concentration was slightly, but significantly higher (89.9 +/- 28.5 microM) during infusion of regimen I than regimen II (66.5 +/- 19.8 microM), but values did not differ significantly from values observed in normal, orally fed premature infants (107 +/- 36 microM). No significant differences were noted in either plasma or erythrocyte aspartate concentrations, or in erythrocyte glutamate concentration. Since plasma and erythrocyte levels of dicarboxylic amino acids remained within the normal range, the data indicate no hazard to young infants from infusion of dicarboxylic amino acids at this level.
It has been suggested that monosodium L-glutamate (MSG) addition to meals would significantly increase plasma glutamate concentrations compared to values noted after ingestion of protein-bound glutamate. To test this hypothesis, plasma amino acid concentrations were measured in six normal adults ingesting a ready-to-feed liquid meal (Sustagen) containing added MSG at 0, 100, and 150 mg/kg body weight (Latin square design), and compared to plasma values noted after ingestion of 150 mg/kg body weight MSG in water. The mean (+/- SD) peak plasma glutamate concentrations after ingestion of meals providing 0, 100, and 150 mg/kg body weight MSG were 6.64 +/- 1.99, 11.2 +/- 4.89 and 10.8 +/- 3.10 mumol/dl, respectively. Erythrocyte glutamate concentrations were unchanged after each meal. Peak plasma glutamate concentrations after ingestion of meals with added MSG were similar to those noted in normal adults ingesting a similar quantity of protein-bound glutamate. In contrast, ingestion of MSG in water (150 mg/kg body weight) markedly increased the mean (+/- SD) peak plasma glutamate concentration to 71.8 +/- 35.7 mumol/dl. Similarly, the area under the plasma glutamate concentration-time-curve was significantly higher. MSG ingestion with meals results in lower plasma glutamate concentrations than ingestion of equivalent doses in water.
In previous studies, plasma glutamate concentration was lower when equivalent doses of monosodium L-glutamate (MSG) were given with a ready-to-feed liquid formula meal (Sustagen; 0.4 g protein, 1.1 g carbohydrate, 0.06 g fat, 6.6 kcal energy/kg body weight) rather than in water. This difference was suggested to reflect a carbohydrate effect on mucosal cell glutamate metabolism. To test this hypothesis, a large dose of monosodium L-glutamate (150 mg/kg body weight) dissolved in water, with or without added carbohydrate, was administered to eight healthy adult subjects. Carbohydrate was administered at 1.1 g/kg body weight in the form of partially hydrolyzed corn starch (Polycose). In the absence of carbohydrate, the mean (+/- SD) peak plasma glutamate concentration was 59.4 +/- 46.5 mumol/dl, and the incremental area under the plasma glutamate concentration time curve was 3391 +/- 2360 mumol/(dl x min). The addition of carbohydrate to the glutamate solution significantly decreased (p = 0.001) both the mean peak plasma glutamate concentration (7.18 +/- 3.48 mumol/dl) and the incremental area under the plasma glutamate concentration-time-curve (451 +/- 20.8 mumol/(dl x min). Erythrocyte glutamate and aspartate concentrations were not affected by glutamate loading in either test. Delayed gastric emptying did not account for the carbohydrate effect. Carbohydrate is postulated to serve as a pyruvate source for mucosal cells, facilitating the transamination of glutamate and its subsequent metabolism. This process would reduce the release of glutamate to the peripheral circulation.
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.
Intravenous solutions of glucose oligosaccharides are potential sources of carbohydrate-derived energy for patients requiring intravenous feeding. Relatively little is known about utilization of glucose oligosaccharides linked by beta-glucosidic bonds. We compared the utilization of maltose (alpha-D-glucosyl-1,4-D-glucose) and beta-cellobiose (beta-D-glucosyl-1,4-D-glucose) when administered intravenously (19 g per day) to young pigs for a 5-day period. Animals infused with maltose excreted 15% of the infused disaccharide over the 5-day infusion period. No evidence of maltose accumulation was noted in plasma, and kidney morphology was normal. Animals infused with beta-cellobiose excreted 95% of the infused disaccharide in the urine. The mean (+/- SD) plasma total glucose concentration increased significantly over base-line values of 114 +/- 39 mg/dl to a value of 180 +/- 28 mg/dl during cellobiose infusion, indicating accumulation of cellobiose in body water. Kidney morphology in cellobiose-infused animals was normal. Intravenously infused beta-cellobiose is poorly utilized by the pig when compared with the utilization of its alpha-1,4 linked isomer, maltose.