George L. Baker

Outcome at ages 1, 3, and 5 years of children born to diabetic women

A prospective study of infants born to women with diabetes mellitus is reported. The children were examined at birth and followed at 1, 3, and 5 years of age. Medical and psychological information was obtained through follow-up examinations. Intrauterine growth was atypical and there was an increase in neonatal problems and congenital malformations. There was an increased incidence of intellectual delay at 3 and 5 years of age. The presence of acetone in the urine during pregnancy had a significant, adverse effect on intellectual status of the offspring at 5 years of age. Birth weight was negatively related to intellectual status at both 3 and 5 years of age.

Infusion of protein hydrolysates in the newborn infant: plasma amino acid concentrations.

Protein hydrolysate infusions commonly administered to young infants unable to sustain adequate protein intake contain large amounts of glutamate and aspartate. Neurotoxic effects have been reported in other species and were attributed to high doses of these amino acids. Plasma glutamate and aspartate levels in infants treated with such preparations were within normal limits, but other amino acids were markedly below fasting levels. Plasma amino acid levels quickly reflected the amino acid composition of the hydrolysate and some degree of amino acid imbalance resulted when either of the 2 products employed in this study constituted the sole source of protein intake.

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.

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.

Repeated ingestion of aspartame-sweetened beverage: Effect on plasma amino acid concentrations in normal adults

Aspartame (APM) is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of the product might elevate plasma aspartate and phenylalanine concentrations. Eight normal adults (four male, four female) ingested three successive 12-oz servings of APM-sweetened beverage at two-hour intervals. The study was carried out in two parts in a randomized cross-over design. In one study the beverage was not sweetened. In the other, the beverage provided 10 mg APM/kg body weight per serving. Plasma amino acid concentrations were measured throughout the six-hour study period. The addition of APM to the beverage had no significant effect on plasma aspartate concentration. APM addition did increase plasma phenylalanine levels 1.64 to 2.05 mumol/dL above baseline values (5.09 +/- 0.82 mumol/dL) 30 to 45 minutes after each dose. However, plasma phenylalanine levels did not exceed normal postprandial values at any time. The data indicate ready metabolism of APMs amino acid content when administered at levels likely to be ingested by individuals who are heavy users of such beverages.

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.

Plasma amino acid concentrations in normal adults ingesting aspartame and monosodium l-glutamate as part of a soup/beverage meal

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.

Monosodium Glutamate: Effect on Plasma and Breast Milk Amino Acid Levels in Lactating Women

Summary Recent studies describing the occurrence of specific neurotoxic effects in suckling animals of several species following oral or subcutaneous administration of large quantities of monosodium glutamate have raised questions regarding the safety of monosodium glutamate as a food additive for pregnant and lactating women. Plasma and breast milk free amino acid levels were measured in lactating women following ingestion of a single 6 g load of monosodium glutamate administered with either water or Slender. Small increases in plasma glutamate, aspartate and alanine levels were noted. However, little change was noted in breast milk amino acid levels. These data indicate that little, if any, of the administered load is concentrated in the milk.

Use of vitamin K1 in pregnancy

In general, from this double blind study of 204 infants it appeared that prenatal oral administration of vitamin K 1 exerted a beneficial effect on the relative deficiency of prothrombin that normally exists in the newborn infant. There was no evidence of undesirable side effects from doses of vitamin K 1 employed in this study. Bilirubin levels in the newborn infants receiving vitamin K 1 were not increased over the values in the placebo group. It is not possible to conclude from these data that such treatment is to be generally endorsed.

Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria.

It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.