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Biomedical subjects

L J Filer

Publications and source records attributed to L J Filer.

At least 55 records · Page 3Linked to original sources

Effect of aspartame loading on plasma and erythrocyte free amino acid concentrations in one-year-old infants.

Aspartame is a new dipeptide sweetener. It has been suggested that infants metabolize its constituent amino acids (aspartate and phenylalanine) less well than adults. To test this hypothesis, 24 1-year-old infants were administered 34, 50 and 100 mg/kg body weight aspartame in cherry-flavored beverage mix. Plasma amino acid concentrations and the areas under the plasma concentration-time curves (AUC) were determined and were compared with values in adults administered equivalent doses. The doses studied include the 99th percentile of projected ingestion for adults (34 mg/kg), a very high use dose (50 mg/kg body weight), and a potentially abusive dose (100 mg/kg body weight). Plasma aspartate concentrations did not change significantly (P greater than 0.05) at aspartame doses of 34 and 50 mg/kg body weight, but did increase significantly at the 100 mg/kg body weight dose. The change over base line was similar in infants and adults. Aspartame dosing significantly increased both the mean peak plasma phenylalanine concentration and the plasma phenylalanine AUC value in proportion to dose. Mean (+/- SD) peak plasma phenylalanine concentrations in infants were 9.37 +/- 1.44, 11.6 +/- 4.44 and 22.3 +/- 11.5 mumol/100 ml at aspartame doses of 34, 50 and 100 mg/kg body weight, respectively. Values in infants were similar to those noted in adults. The data do not support the suggestion that infants metabolize the amino acids of aspartame less well than adults.

Adult↗

Blood methanol concentrations in one-year-old infants administered graded doses of aspartame.

Blood methanol concentrations were measured in 24 1-year-old infants administered aspartame, a dipeptide methyl ester sweetener. The doses studied included a dose projected to be the 99th percentile of daily ingestion for adults (34 mg/kg body weight), a very high use dose (50 mg/kg body weight) and a dose considered to be in the abuse range (100 mg/kg body weight). Blood methanol values in infants were compared to values observed previously in adults administered equivalent doses of aspartame. Methanol concentrations were below the level of detection (0.35 mg/dl) in the blood of 10 infants administered aspartame at 34 mg/kg body weight, but were significantly elevated (P less than or equal to 0.05) after ingestion of aspartame at 50 and 100 mg/kg body weight. At the latter doses, mean peak blood methanol concentrations and the area under the blood methanol concentration-time curve increased in proportion to dose. Mean (+/- SEM) peak blood methanol concentration was 0.30 +/- 0.10 mg/100 ml at a 50 mg/kg body weight aspartame dose (n = 6) and 1.02 +/- 0.28 mg/ml at the 100 mg/kg body weight dose (n = 8). Blood methanol values in infants were similar to those observed in normal adults.

Age Factors↗

Plasma amino acid concentrations in normal adults fed meals with added monosodium L-glutamate and aspartame.

Aspartame is a dipeptide sweetener containing aspartate. It has been suggested that aspartame addition to meals containing large amounts of monosodium L-glutamate (MSG) would result in a rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid--induced toxicity. Sic normal adult subjects were fed three hamburger and milk shake meals providing protein at 1 g/kg body weight in a Latin square design. One meal had no additions, the second provided MSG at 150 mg/kg body weight, and the third provided MSG at 150 mg/kg body weight and aspartame at 23 mg/kg body weight. The addition of MSG alone significantly increased plasma glutamate + aspartate concentration above values noted after ingestion of the meal alone. Aspartame addition to meals already containing MSG did not further significantly increase plasma glutamate + aspartate concentration above values noted when only MSG was added. However, aspartame addition did significantly increase the mean plasma phenylalanine concentration above values noted after ingestion of the meal alone or the meal with added MSG, reflecting aspartame's phenylalanine content. The data do not support the suggestion that aspartame addition to high protein meals already containing large amounts of MSG, will promote a rapid and dangerous rise in plasma glutamate and aspartate concentrations.

Adult↗

Effect of sampling site on plasma amino acid concentrations of infants: effect of skin amino acids.

Plasma taurine, aspartate, threonine, serine, glycine, alanine, valine, leucine, tyrosine, phenylalanine, tryptophan, lysine, histidine, and ornithine concentrations are significantly greater (p less than 0.05, "Student's" t test) in blood samples obtained by conventional heel skin puncture techniques from 1-yr-old infants than values in venous plasma. Differences in plasma concentrations of taurine, aspartate, serine, glycine, and ornithine were particularly striking, with levels in plasma collected from the heel being 1.6 to 6.7 times higher than levels in venous plasma. These increased plasma amino acid concentrations were shown to result primarily from contamination of the plasma with amino acids present on the skin surface. Thorough washing and stimulation of blood flow to the heel by warming prior to skin puncture reduced observed differences. Plasma amino acid concentrations of blood samples obtained by conventional heel skin puncture procedures can be "normalized" to venous values through the use of data on the amino acid composition of heel skin washings.

Amino Acids↗

Effect of aspartame plus monosodium L-glutamate ingestion on plasma and erythrocyte amino acid levels in normal adult subjects fed a high protein meal.

It has been suggested that aspartame addition to meals already containing large amounts of monosodium L-glutamate would result in an early rapid rise in plasma glutamate and/or aspartate concentrations and increase the potential for dicarboxylic amino acid-induced toxicity. Six normal adult subjects were fed hamburger and milk shake meals providing protein at 1 g/kg body weight in a randomized cross-over design. One meal had no additions while the other contained added monosodium L-glutamate and aspartame (each present at 34 mg/kg body weight). The addition of aspartame plus glutamate had little effect on either plasma or erythrocyte concentrations of glutamate or aspartate beyond those arising from the meal itself. Plasma phenylalanine concentrations were significantly higher (p less than 0.05, paired t test) after ingestion of meals containing aspartame plus glutamate reflecting the increased phenylalanine load.

Adult↗

Plasma and erythrocyte amino acid levels in normal adult subjects fed a high protein meal with and without added monosodium glutamate.

It has been suggested that the addition of free glutamate to meals already containing large amounts of protein-bound glutamate would produce an early rapid rise in plasma glutamate and/or aspartate concentrations, increasing the potential for glutamate-induced adverse effects. Normal adult subjects were fed a hamburger and milk shake meal providing protein at 1 g/kg body weight with and without added monosodium L-glutamate (34 mg/kg body weight). The addition of glutamate to the meal at this level had no significant effect on either plasma or erythrocyte concentrations of glutamate or aspartate beyond those arising from the meal itself. Free glutamate added to a hamburger and milk shake meal at this level is rapidly metabolized and does not elevate plasma concentrations of these dicarboxylic amino acids.

Adult↗

Plasma and urinary methionine levels in one-year-old infants after oral loading with L-methionine and N-acetyl-L-methionine.

N-acetyl-L-methionine has been proposed as a replacement for methionine in supplementing food products low in this amino acid. Previous studies in adult subjects administered equimolar quantities (0.0605 mmoles/kg body weight) of L-methionine and N-acetyl-L-methionine showed equivalent overall release of methionine to the blood as judged by area under the plasma methionine time--absorption curve. In the present study, similar doses (0.0605 mmoles/kg body weight) of L-methionine and N-acetyl-L-methionine were administered to fasting 1-year-old infants in a randomized crossover design. The two compounds produced an equivalent overall release of methionine to the blood as judged by plasma methionine concentrations and by the area under the plasma methionine concentration--time curves. No evidence was obtained that indicated release of N-acetyl-L-methionine to plasma or its excretion in urine after loading. However, peak plasma methionine concentrations, and the areas under the plasma methionine concentration--time curves for infants were approximately one-half the values observed in normal adults administered equimolar doses of each compound on a per kilogram body weight basis. The data suggest more rapid metabolism of methionine and N-acetyl-L-methionine by infants than adults.

Age Factors↗

Utilization of intravenously administered glucose-oligosaccharides in growing miniature pigs.

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 29 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 of 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 (greater than or equal to 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 indicated that glucose oligosaccharide solutions were less effective than glucose as an energy source.

Animals↗

Plasma phenylalanine levels in phenylketonuric heterozygous and normal adults administered aspartame at 34 mg/kg body weight.

Following administration of aspartame (34 mg/kg body wt) in orange juice, plasma concentrations of free amino acids were measured in 12 female subjects known to be heterozygous for phenylketonuria and 22 normal subjects (12 male, 10 female). No change in fasting plasma aspartate concentrations were noted after aspartame loading in either group. In normal male subjects, the mean (+/-S.D.) plasma phenylalanine concentration increased from a fasting value of 5.86 +/- 1.25 mumol/dl. Plasma phenylalanine levels in normal female subjects increased from a mean fasting concentration of 4.83 +/- 0.84 mumol/dl to a men peak value of 8.95 +/- 1.49 mumol/dl suggesting a more rapid absorption, metabolism, and/or clearance of phenylalanine by females. In female heterozygous subjects, the mean peak plasma phenylalanine concentration was significantly higher than in normal females. Plasma phenylalanine values increased from a mean fasting value of 5.92 +/- 1.51 mumol/dl to a mean peak value of 15.1 +/- 4.76 mumol/dl. Similarly, the area under the plasma phenylalanine concentration-time curve was significantly greater in heterozygous female subjects (21.36 +/- 5.10 IU) than in normal female subjects (10.84 +/- 2.32 IU). However, peak plasma phenylalanine levels were well below those associated with toxic effects in all cases.

Adult↗

Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame.

Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.

Adult↗

Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame.

Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.

Adult↗

The role of vitamin E in the nutrition of premature infants.

Vitamin E (alpha-tocopherol) has been credited with a variety of beneficial effects in the premature newborn infant. It has been thought that deficiency of vitamin E is at least partly responsible for the anemia which often occurs 4 to 6 wk after premature birth, and routine dietary supplementation with vitamin E is frequently recommended. However, critical analysis reveals that published controlled studies of vitamin E supplementation do not agree on the magnitude or even the existence of this protective effect against anemia. Analysis of commonly used feeding practices suggests that the dietary ratio of alpha-tocopherol to polyunsaturated fatty acids is generally sufficient to prevent manifestations of vitamin E deficiency without supplementation. Large parenteral doses of vitamin E have been purported to protect premature infants exposed to oxygen-enriched environments and mechanical ventilation from the complications of retrolental fibroplasia and bronchopulmonary dysplasia. Subsequent studies, however, have not yet substantiated encouraging early reports of these protective effects. At present, there seems to be no clearly established need for supplementing the premature infant's usual dietary intake of vitamin E.

Adult↗

Effect of aspartame and sucrose loading in glutamate-susceptible subjects.

It has been postulated that individuals reporting an idiosyncratic symptom response after glutamate ingestion might also experience such symptoms after aspartame ingestion. Such sensitive subjects might have been missed in earlier studies of aspartame. In the present study, six subjects reporting various symptoms after glutamate ingestion, but not after placebo, were administered aspartame (34 mg/kg body weight) or sucrose (1 g/kg body weight) dissolved in orange juice in a randomized, cross-over, double-blind study. No subject reported symptoms typical of a glutamate response after either sucrose or aspartame loading. One subject reported slight nausea approximately 1.5 h after aspartame ingestion, but indicated that the symptoms were not those of a glutamate response. Plasma phenylalanine and aspartate levels were similar to those noted in normal subjects administered identical doses of aspartame. The data indicate no effect of aspartame loading in glutamate-susceptible subjects.

Aspartame↗

Utilization of intravenously administered maltose by growing miniature pigs.

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.

Animals↗

Aspartame administration to the infant monkey: hypothalamic morphology and plasma amino acid levels.

Infant monkeys received 2 gm/kg body weight of aspartame (APM) or 2 gm/kg body weight APM plus 1 gm/kg body weight monosodium glutamate (MSG) by gastric tube. Blood samples were obtained at intervals over the ensuing 4 hours and analyzed for amino acid levels. At this time, each infant was perfused with glutaraldehyde. The hypothalamus was embedded in plastic and then serially sectioned at 1 mu. Hypothalamic morphology was normal in all eight infants given 2 gm/kg body weight APM and in the six infants given 2 gm/kg body weight APM plus 1 gm/kg body weight MSG. By light microscopy, no pycnotic nuclei, neuronal degeneration, or dendritic swelling was noted. In both experimental and control brains, localized areas of poor perfusion exhibited abnormal morphology. Elevated plasma levels of aspartate, glutamate, and phenylalanine indicated that the test compounds were administered and absorbed. Variable rates of absorption were evident, probably due to the necessity of administering APM as a slurry, due to its low solubility. On the basis of blood absorption curves, it appears that infant monkeys metabolize aspartate and glutamate and phenylalanine somewhat more rapidly than man. It is concluded that APM given alone or with MSG, in large acute doses, does not result in hypothalamic damage in the newborn monkey.

Amino Acids↗

Plasma methionine levels in normal adult subjects after oral loading with L-methionine and N-acetyl-L-methionine.

The biological quality of soy protein isolates is limited by methionine content but can be enhanced by methionine addition. Since supplemental methionine may undergo chemical modification during processing, producing objectionable odors, N-acetyl-L-methionine has been proposed as a methionine replacement. Plasma and erythrocyte methionine levels and the area under the plasma and erythrocyte methionine absorption curve were compared in five normal adult subjects administered equimolar quantities (0.0605 mmoles/kg) of L-methionine and N-acetyl-L-methionine. The two compounds produced an equivalent overall release of L-methionine to the blood as judged by the area under the plasma and erythrocyte methionine time-absorption curves. There was a difference in the early part of both absorption curves (15 to 45 minutes), with plasma and erythrocyte levels higher after L-methionine administration than after N-acetyl-L-methionine administration. However, this difference was only statistically significant at 15 minutes (P = 0.03). Gastric emptying did not account for this difference apparently reflecting a slower rate of absorption of N-acetyl-L-methionine by mucosal cells. No evidence was obtained that indicated release of N-acetyl-L-methionine to the plasma or its excretion in urine after loading. The data are consistent with previous data showing L-methionine and N-acetyl-L-methionine to be equivalent sources of methionine.

Adult↗