Monosodium glutamate metabolism in the neonatal monkey

Stegink, L. D.; Reynolds, W. Ann; Lj, Filer; Pitkin, Roy M.; Boaz, DP; Brummel, MC

doi:10.1152/ajplegacy.1975.229.1.246

Cited by 47 publications

(9 citation statements)

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“…Animals have been sacrificed 3-6 h after administration, because of the transient nature of MSG-induced arcuate lesions seen in rodents. In newborn monkeys, fasting plasma GLU concentrations are around 10 nmol/mL, and rise to peak values some 17-fold (1,000 mg/kg bw dose) to 33-fold (4,000 mg/ kg bw dose) above baseline values within 1 h of oral administration [32]. Such enormous increases in plasma GLU concentrations are in the range of those observed in rodents (see above).…”

Section: Non-human Primate and Human Studiesmentioning

confidence: 84%

“…In rodents, the increase needed to produce arcuate lesions is typically in the 30-50-fold range [14,45]. In monkeys, large doses of MSG produce increases of 17-fold (1,000 mg/kg bw, by stomach tube) and 33-fold (4,000 mg/kg bw, by stomach tube), but are associated with no arcuate lesions [26,32]. Additionally, a dose of MSG that stimulated LH secretion in monkeys (150 mg/kg, given intravenously) produced a 50-fold rise in plasma GLU concentrations [44].…”

Section: How High Do Plasma Glu Concentrations Increasementioning

confidence: 99%

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Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

Fernstrom¹

2018

Ann Nutr Metab

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The non-essential amino acid glutamate participates in numerous metabolic pathways in the body. It also performs important physiologic functions, which include a sensory role as one of the basic tastes (as monosodium glutamate [MSG]), and a role in neuronal function as the dominant excitatory neurotransmitter in the central nervous system. Its pleasant taste (as MSG) has led to its inclusion as a flavoring agent in foods for centuries. Glutamate’s neurotransmitter role was discovered only in the last 60 years. Its inclusion in foods has necessitated its safety evaluation, which has raised concerns about its transfer into the blood ultimately increasing brain glutamate levels, thereby causing functional disruptions because it is a neurotransmitter. This concern, originally raised almost 50 years ago, has led to an extensive series of scientific studies to examine this issue, conducted primarily in rodents, non-human primates, and humans. The key findings have been that (a) the ingestion of MSG in the diet does not produce appreciable increases in glutamate concentrations in blood, except when given experimentally in amounts vastly in excess of normal intake levels; and (b) the blood-brain barrier effectively restricts the passage of glutamate from the blood into the brain, such that brain glutamate levels only rise when blood glutamate concentrations are raised experimentally via non-physiologic means. These and related discoveries explain why the ingestion of MSG in the diet does not lead to an increase in brain glutamate concentrations, and thus does not produce functional disruptions in brain. This article briefly summarizes key experimental findings that evaluate whether MSG in the diet poses a threat to brain function.

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Section: Non-human Primate and Human Studiesmentioning

confidence: 84%

Section: How High Do Plasma Glu Concentrations Increasementioning

confidence: 99%

Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

Fernstrom¹

2018

Ann Nutr Metab

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“…Such regression curves based on adult data (4) indicate that an MSG dose of 150 mg/kg body weight, ingested in consomme, bouillon, or tomato juice, would result in a mean peak plasma glutamate concentration of 50 to 60 pmol/dl. This projected plasma glutamate plus aspartate concentration (50 to 60 pmol/dl) approaches the threshold value associated with toxicity in the infant mouse, but is still far below the no effect level of 450 pmol/dl observed in the infant nonhuman primate (37,42). If, on the other hand, infants metabolize larger doses of MSG more slowly than adults, the plasma glutamate concentration response will be larger in infants than in adults.…”

Section: Discussionmentioning

confidence: 76%

“…If this factor is applied to humans, such projections indicate that infants ingesting 150 mg MSG/kg body weight might have a mean peak plasma glutamate concentration of 100 to 120 pmol/dl. This putative plasma glutamate concentration would exceed the threshold value associated with toxicity in the infant mouse, but would still be within the no effect plasma glutamate range in the infant nonhuman primate (37,42).…”

Section: Discussionmentioning

confidence: 91%

“…The use of glutamate as a food additive has been controversial. However, four other laboratories were unable to find lesions in infant monkeys given equally large doses of MSG (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). The failure of these groups to observe lesions in neonatal nonhuman primates did not reflect a failure of the glutamate load to produce elevated plasma glutamate concentrations (37,42).…”

Section: Discussionmentioning

confidence: 98%

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Plasma Glutamate Concentrations in 1-Year-Old Infants and Adults Ingesting Monosodium L-Glutamate in Consommé

et al. 1986

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ABSTRACT. This study tested the hypothesis that infants metabolize glutamate more slowly than adults. Eight l-yrold infants ingested 160 ml of a beef consommi: 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 consomme. In adults, mean (+ SD) peak plasma glutamate concentrations were 5.59 f 1.56, 10.2 + 2.08, and 17.0 f The ability of human infants to metabolize MSG has been one area of concern in considering glutamate's safety as a food additive. Olney (1-3) postulated that human infants metabolized dicarboxylic amino acids more slowly than adults, and projected theoretical plasma glutamate concentrations for infants at much higher values than those for adults following glutamate ingestion.The present study directly tested this hypothesis by measuring the plasma glutamate and aspartate response in 1-yr-old infants fed a beef consommi containing graded doses of MSG. The results of these studies were compared with previously reported (4) plasma glutamate and aspartate values in normal adults administered equivalent doses of MSG in the same consomm6. MATERIALS AND METHODSEight infants (four male, four female) were studied. The proposed study was explained to at least one of the parents and informed, written consent was obtained. The protocol of the study was reviewed and approved by the Committee on Research Involving Human Subjects of the University of Iowa.Each child ingested 160 ml of beef consommC providing 0,25, and 50 mg/kg body weight of added MSG in a balanced crossover design. Each infant was randomly assigned to receive consommi providing either 0 or 25 mg MSG/kg body weight, followed by the other dose at least 1 wk later. After these two tests had been completed and the results evaluated, each infant ingested consommi providing MSG at 50 mg/kg body weight. All tests were begun at 0800 h following an overnight fast.The monohydrate of monosodium L-glutamate was purchased from a local grocery store (Accent International, Pet Incorporated, St. Louis MO). The soup was prepared from a special beef consommk base supplied by the Ajinomoto Company (Tokyo, Japan). The composition of the soup base is shown in Table 1. As noted in Table 1, 160 ml of reconstituted soup contained 37 mg of free glutamate, for a mean dose of 4.1 mg/kg body weight. Thus, the true final doses of MSG studied in these infants were 4.1, 29.1 and 54.1 mg/kg body weight.Each infant was assigned by random allocation into one of two equal groups that differed with respect to time of blood sampling. Since only four blood samples were obtained from each infant after dosing, two different sampling schedules were utilized so as to obtain samples during the entire absorptive period. Blood samples at each dose level were obtained from four infants at 0, 30, 60, and 120 min After ingestion of the consommG Blood samples from ...

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

et al. 1980

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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.

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Monosodium glutamate metabolism in the neonatal monkey

Cited by 47 publications

References 0 publications

Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

Plasma Glutamate Concentrations in 1-Year-Old Infants and Adults Ingesting Monosodium L-Glutamate in Consommé

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

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