Monosodium Glutamate Intake Research Articles

Circadian variations in plasma and erythrocyte concentrations of glutamate, glutamine, and alanine in men on a diet without and with added monosodium glutamate.

Variations in plasma and erythrocyte concentrations of glutamate, glutamine, and alanine during the day were studied in 10 healthy men fed ordinary Taiwanese meals, first without and, 1 week later, with monosodium glutamate (MSG) added. MSG at a level of 15, 40, and 45 mg/kg (total, 100 mg/kg/d) was added, respectively, to the breakfast, lunch, and dinner meals. Heparinized blood samples were collected over 24 hours with 1- to 3-hour intervals. In both trials, plasma glutamate concentrations increased significantly after lunch and dinner. Although the circadian variations of plasma glutamate were small (between 32 and 53 micromol/L), the levels nevertheless varied significantly as a function of the time of day in both trials. Considering that the dietary intake of glutamate was high when MSG was added, the low plasma glutamate concentration over 24 hours indicates that glutamate is actively metabolized. On the other hand, the concentrations of erythrocyte glutamate (507 to 631 micromol/L) and glutamine (427 to 613 micromol/L) did not show a significant postprandial increase or circadian variation. Nevertheless, the concentration of plasma glutamine (539 to 657 micromol/L) varied significantly as a function of time in both trials. The plasma concentration of alanine (274 to 494 micromol/L) increased significantly after each meal and decreased significantly from 2:00 to 5:00 AM in both trials. Both plasma and erythrocyte alanine concentrations varied significantly as a function of time. These results show that the substantial amount of MSG intake had no apparent effect on the circadian variation profiles of blood glutamate, glutamine, and alanine.

Monosodium glutamate sensitivity in asthma

Background: Questions have been raised since the early 1980s about monosodium glutamate (MSG) and provocation of asthma. Because MSG is widely available as a chemical in both natural foods and as an additive in many prepared foods, the need to define the relationship of MSG to asthma is of great importance. Objective: The purpose of this study was to determine whether MSG ingestion induces asthma attacks in asthmatic subjects. Methods: With single-blind, placebo-controlled screening challenges, 100 subjects with asthma (30 subjects with a history of Oriental restaurant asthma attacks; 70 subjects with a negative history) were challenged with 2.5 g of MSG. A total of 78 patients were proved to have aspirin-sensitive asthma. Results: No patient had a significant fall in FEV 1 value or the development of asthma symptoms during the MSG challenge. The mean change in FEV 1 with MSG challenge was no different from that of placebo challenge. Subjects with an MSG-positive history showed no significant percent decrease in FEV 1 values after placebo challenges compared with MSG 2.5 g oral challenge ( P = .28). In the group with an MSG-negative history, there was no statistical difference in the change in lowest FEV 1 values between the placebo and MSG challenges ( P = .44). The exact 1-sided 95% confidence interval (CI) for the probability of MSG sensitivity in individuals with aspirin-sensitive asthma (negative history) is 0% to 0.04%. When combined with previous studies that did not demonstrate MSG-provoked asthma, the 95% CI is 0% to 0.03%. For patients with an MSG-positive history, the exact 1-sided 95% CI for the probability of MSG sensitivity in this study was 0% to 0.07%, which is somewhat wider because of the smaller sample size. Conclusions: MSG challenges in subjects with and without a perceived sensitivity to MSG failed to induce signs or symptoms of asthma. Therefore in view of the poorly conducted studies that proposed that MSG induced asthma and the subsequent studies that failed to confirm those findings, it is important to maintain a healthy skepticism about the existence of MSG sensitivity in individuals with asthma. (J Allergy Clin Immunol 1999;104:305-10.)

The monosodium glutamate symptom complex: Assessment in a double-blind, placebo-controlled, randomized study

Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.

Extracellular glutamate levels in the hypothalamus and hippocampus of rats after acute or chronic oral intake of monosodium glutamate

Using brain microdialysis we studied the effect of high doses of monosodium glutamate (MSG) on the extracellular concentration of glutamate in the hypothalamus and in the hippocampus of freely moving rats. MSG at 4 g/kg (40% solution) given by gavage caused a significant increase in plasma (5.3 ± 0.4-fold, P < 0.01) and extracellular glutamate in the hippocampus (4.2 ± 0.6-fold, P < 0.01) and in the hypothalamus (8.9 ± 1.7-fold, P < 0.01) compared to control rats receiving a 40% sucrose solution (10 ml/kg). The peak increase was found within 40 min after MSG administration then declining to baseline in the next 80 min. No changes were found in glutamate tissue concentrations. Twenty-one days after ad libitum MSG intake with the diet (approximately 4 g/kg) no changes were found, in plasma, in extracellular and tissue concentration of glutamate in the hypothalamus compared to rats fed with a normal diet. Glutamate release induced by 200 mM KC1 was not modified as well. Histological analysis of Nissl-stained brain tissue slices did not reveal any obvious cell loss in the hippocampus and hypothalamus after acute or chronic MSG administration.

Effects on metabolic and hormonal parameters of monosodium glutamate (umami taste) ingestion in the rat

Umami taste appears to signal, at the gustatory level, the intake of proteins, therefore the working hypothesis was: does umami taste of a monosodium glutamate (MSG) solution elicit changes in both glucagon and insulin release, similar to those elicited by aminoacids, and consequently, changes in plasma glucose and in overall cellular metabolism? In a first experiment, rats were equipped with indwelling jugular and oral catheter and serial samplings were made in the free moving, undisturbed rat before and after an oral or IV infusion of MSG (0.05M). None of the plasma parameters showed any significant response. In a second experiment, energy expenditure was monitored by means of an original computer-based calorimeter capable of calculating, besides the classical parameters, resting metabolism in a moving animal (designated by background metabolism). The addition of MSG to a low calorie, low-protein meal did not modify background metabolism or respiratory quotient. Therefore MSG ingestion does not by itself affect plasma levels of hormones of glucose and protein metabolism, total metabolism rate, or nutrient utilization. However, examination of individual data and those from a pilot experiment for future work suggests that MSG becomes an efficient metabolic effector if added to a caloric diet, and so enhances proper thermogenesis of macronutrients.

The effect of L-glutamic acid on airway function and reactivity in the rabbit.

The ingestion of monosodium glutamate in sensitive individuals has been reported to cause severe asthma. We therefore studied the effects of L-glu on airway function and histamine (H) responsiveness in the rabbit. Histamine dose response curves (HDR's) were performed by measuring total lung resistance (RL) after inhalation of saline and increasing concentrations of H (1-30 mg/ml). The concentration of H producing a 20% increase in RL (PC20H) was obtained by interpolation. To assess the effects of L-glu, 8 rabbits were infused with L-glu (0.2 g/kg/hr) or saline in random order (14 days apart) for 4 hours followed by an HDRC. To look at possible late effects, a repeat HDRC was also performed in 6 rabbits 12 hours after completion of the L-glu infusion. In order to see whether rabbits rendered hyperresponsive responded to L-glu, the above protocol was performed in 7 rabbits following the inhalation of 3 micrograms of the activated complement fragment C5a des Arg. The L-glu infusions increased the plasma levels approx. ten-fold (mean +/- SEM 0.119 +/- 0.012 base-line, 1.272 +/- 0.061 mmol/l post infusion). L-glu did not increase the PC20H or baseline RL in either the normal rabbits at 4 or 12 hours or in the C5a des Arg treated rabbits at 4 hours. It is concluded that L-glu does not cause bronchoconstriction or an increase in airway responsiveness to H in the rabbit.

Taste effects of ‘umami’ substances in hamsters as studied by electrophysiological and conditioned taste aversion techniques

Behavioral and electrophysiological experiments were performed to examine whether or not the taste of ‘umami’ substances such as monosodium glutamate (MSG), disodium 5′-inosinate (IMP), and disodium 5′-guanilate (GMP) is really unique in hamsters. When the animals were conditioned to avoid ingestion of MSG (or IMP) or their mixture by pairing its ingestion with an i.p. injection of LiCl, suppression of drinking generalized to IMP (or MSG), GMP, NaCl, and other sodium salts. Suppression of drinking after conditioning to NaCl generalized to MSG, IMP, GMP, and inorganic sodium salts. These learned aversions to umami substances and sodium salts were abolished by bilateral deafferentation of the chorda tympani, but were not affected by destruction of the bilateral glossopharyngeal nerves. The integrated whole-nerve responses of the chorda tympani to MSG, IMP, and NaCl were similar to each other, consisting of the initial dynamic phase and the following tonic phase. Synergism of chorda tympani responses to a mixture of MSG and IMP was not observed. Across-fiber response patterns of the chorda tympani for MSG, IMP, or their mixture were very similar to that for NaCl. Even the high concentrations of umami substances (0.3 M MSG, 0.3 M IMP, and the mixture) did not elicit any detectable responses in the glossopharyngeal nerve. These results suggest that the taste of umami substances is not unique in the hamster, but is similar to that of sodium salts, and is mediated exclusively via the chorda tympani.

Kinetics of monosodium glutamate in human volunteers under different experimental conditions

The kinetics of glutamic acid (GA) in plasma was studied in human volunteers after administration of monosodium glutamate (MSG) at different doses—43 mg/kg (3 g/70 kg) and 64 mg/kg (4.5 g/70 kg)—and in bouillon solutions of different concentrations (1.5–3.5%). MSG was administered to the subjects either during fasting or immediately after a standard meal. In the fasted subjects MSG administration caused a dose-dependent increase in plasma GA levels. In contrast, ingestion of MSG with a meal did not result in any significant increases in plasma GA levels in comparison with the wide variations observed in plasma GA after ingestion of a meal without added MSG.

Effects of monosodium glutamate.

Monosodium glutamate (MSG) is a possible precursor of L-glutamic acid ( 9 ) . Literature suggests glutamic acid to be a central nervous system excitant (6 , 7, 9 ) . Other behavioral and psychological effects of glutamic acid on animals include: (a ) hyperemotionality and increase in biting behaviors, ( b ) seizures (1, 2, 4 ) . and (c) hypothalamic brain lesions (3, 5, 8 ) . Several experiments have been conducted for exploratory reasons and for support of findings reported previously. Samples used in each of the experiments included: ( a ) Exp. 1 : 5 male rats, (b) Exp. 2 : 10 male rats ( 5 treaunent, 5 control), (c) Exp. 3: 4 male rats, ( d ) Exp. 4: 5 male rats, (e) Exp. 5 : 5 male rats. All treatment groups were administered MSG adulterated food or water. Exp. 1, performed to determine the amount of MSG rats would consume voluntarily per day, resulted in an average daily intake of 500. mg. MSG. Exp. 2, conducted to determine effects of MSG on emotionality and biting behaviors, indicated no significant variance, though there was some suggestion that biting was affected. Exps. 3, 4, and 5 were conducted to assess effects of MSG on activity level and to observe seizurc activity during MSG treatmenr In Exp. 3 some increase in activity was found, however, analysis of variance indicated that this wss not significant. A significant increase in activity level was found after ingestion of MSG in Exps. 4 and 5; activiry level increased further during follow-up in Fxp. 4. Other behaviors observed during treatment were: decrease of grooming, increase in water and food consumption, tremors and convulsions, increase in bitin and reduction of sleep time. The samples were small, and the e f t a s variant. Therefore, results should be considered cautiously. Significant increases in activity might support previous data; further follow-up increases in activity possibly indicate lasting effects of MSG. Results did not support hyperemotionalig, however, increase in biting is suggestive. The presence of seizures and tremors confirms those found in previous reports. Finally apparent decrease in sleep and grooming during treatment mighr support MSG as a psychic energizer. The work is exploratory. Funher research on the effects of MSG is needed.

Hypothalamic morphology following ingestion of aspartame or MSG in the neonatal rodent and primate: a preliminary report.

Neonatal mice received oral doses of monosodium glutamate (MSG) at levels of 0.25, 0.5m 1.0, 2.0, and 4.0 g/kg or aspartame at levels of 0.5, 1.0, 1.5, and 2.0 g/kg. Hypothalamic lesions were encountered at dose levels equal to or exceeding 0.5 g/kg (MSG) and 1.0 g/kg (aspartame). Aspartame administration resulted in a much smaller hypothalamic lesion than did equal dosages of MSG. Infant monkeys received MSG (1-4 g/kg) or aspartame (2 g/kg) by stomach tube. Hypothalamic morphology remained normal at both the microscopic and ultrastructural level. Thus, in contrast to the neonatal rodent, the neonatal primate is able to cope either metabolically or at the level of the blood-brain barrier with excessive amino acid loads.

Glial changes in the progress of a chemical lesion. An electron microscopic study.

The response of non-neuronal cells in the brain to monosodium glutamate (MSG) was studied in the neonatal mouse brain. Neurons rapidly degenerate in this chemically-induced lesion, and the glia reflect and respond to their early pyknosis and death. Astrocytic glia exhibit the most profound responses in the form of degenerative nuclear and cytoplasmic changes within 15 to 20 minutes after ingestion of MSG. After 6 to 12 hours, a large glial cell population, containing neuronal and synaptic debris, can be seen. Recovery of severely damaged astrocytes is unlikely. Further, evidence of multiplication of uninjured cells to supply this observed repopulation was found. Microglia start to engulf debris at 6 to 12 hours and continue this process through at least 48 hours. From 3 to 48 hours, a third cell type, tentatively identified as a Gitter cell, is preminently involved in phagocytosis of neuronal elements. Nuclei of these cells enlarge and their parikarya become vastly expanded in a fashion typical of Gitter cells. These cells appear to represent the transformed microglia. Phagocytosis following a chemical lesion induced by glutamic acid, a neurotransmitter substance, is exceedingly rapid in comparison to that elicited by other types of lesions. Further, endogenous glial cells cope with the cellular debris; no participation in this process by hematogenous cells was observed.

Brain damage in neonatal mice following monosodium glutamate administration: Possible involvement of hypernatremia and hyperosmolality

The effects of glutamic acid hydrochloride, sodium chloride and sucrose administered orally to neonatal mice at levels equimolar and hyperosmolar to those used in obtaining brain damage with a monosodium glutamate (MSG) were examined. Hypernatremia is induced in neonatal mice at the highest dosage of MSG used to elicit neuropathologic changes. Glutamic acid hydrochloride was found to elicit the same pattern of brain lesions as does MSG. High sodium levels therefore, are not necessary to open the bloodbrain barrier for glutamate-induced neuronal lesions. Sodium chloride itself, although not causing lesions in arcuate nucleus, is capable of causing a wide spectrum of damage in neonatal mouse brain at lower levels (0.02–0.05 meq 1) than previously recognized. Glutamic acid and sodium caused brain lesions often in the same structures but their pattern of damage differed, probably as a result of different routes of entry into the brain. Glutamate, or more probably one of its metabolites, damaged cells close to circulating cerebrospinal fluid (CSF), while hypertonic saline apparently egressed into brain tissue from capillaries, arterioles and venules. Neuronal damage following MSG administration tends to radiate inward within structures in contact with circulating CSF. Lesions following sodium chloride ingestion present themselves as foci or bands occurring throughout a given structure. Sometimes neuronal necrosis accompanied hemorrhagic vessels within a structure, a phenomenon not seen following MSG administration. A high rate of animal mortality followed hyperosmolality induced by sucrose loads. Brain shrinkage and extensive vascular dilatation, unaccompanied by marked neuronal dehydration were the major neurological observations. Finally, while neither hyperosmolarity nor hypernatremia is capable of eliciting the patterns of lesions correlated with MSG ingestion, either condition can result in severe vascular changes in the neonatal mouse brain.

Nature and extent of brain lesions in mice related to ingestion of monosodium glutamate. A light and electron microscope study.

The incidence of arcuate neuron damage following 1 to 4 mg/gm oral doses of monosdoium glutamate (MSG) to neonatal mice was studied. The first morphological manifestation of the lesion involved edematous astrocytic glia and pathological changes in neurons close to the median eminence within 15–20 minutes. The sequence of the lesion involved at least three phases: 1) neuronal edema and death, 2) multiple phagocytic cells, viz. a type of “dense” cell and an electron “lucid” cell astrocyte, and 3) proliferation of astrocytic processes. It was noted that at 4 mg doses, the lesions occurred in other areas such as tectum, habenular nuclei, subfornical organ, dorsolateral surface of the thalamus, dentate-hippocampal gyri, cerebral cortex, and in the lower medulla, the nuclei gracilis and cuneatus and area postrema. In all. these structures, the lesion was initiated superficially and radiated inward, suggesting an inflow of the deleterious agent from the cerebrospinal fluid. Comparison of our neuropathological findings with those of others, emphasized the critical aspects of species variation, developmental age, route of administration, time of examination of brain material after dosage and thoroughness of sampling methods.

2359. Rebirth of the MSG syndrome?: Ghadimi, H., Kumar, S. & Abaci, F. (1971). Studies on monosodium glutamate ingestion. I. Biochemical explanation of Chinese restaurant syndrome. Biochem. Med.5, 447

2359. Rebirth of the MSG syndrome?: Ghadimi, H., Kumar, S. & Abaci, F. (1971). Studies on monosodium glutamate ingestion. I. Biochemical explanation of Chinese restaurant syndrome. Biochem. Med.5, 447

Studies on monosodium glutamate ingestion: I. Biochemical explanation of Chinese restaurant syndrome

The signs and symptoms following the ingestion of monosodium glutamate (MSG) were found strikingly similar to those induced by acetylcholine (ACh). The effects of anticholinergic and cholinesterase (ChE) inhibitor support the hypothesis that Chinese restaurant syndrome is a “transient acetylcholinosis”. The pattern of plasma ChE activity in induced acetylcholinemia was strikingly similar to that following MSG ingestion.

“Transient acetylcholinosis”. Cause of Chinese Restaurant syndrome

Both clinical data and biochemical findings in our stuidies suggest that the signs and symptoms following monosodium glutamate (MSG) ingestion represent “transient acetylcholinosis.” Dose-related reactions occurred in 14 volunteers after MSG ingestion on empty stomach, including numbness of neck, heaviness of eyelids and legs, lacrimation, headache, nausea, urgency of urination and defecation, drowsiness, substernal pressure, abdominal discomfort, palpitations and colicky pain. The protean nature of the symptoms, the mode of appearance and recovery, variations in severity, all were remarkably similar to the diffuse, evanescent action of acetylcholine (ACh). In 4 subjects primed with atropine, there was blockage of symptoms even though MSG dose was doubled. On the other hand, prostigmine ( usual dose) given with MSG markedly6 exacerbated symptoms in 4 subjects tested. Others have shown that glutamate is a suitable substrate for ACh synthesis. In 10 subjects receiving 150 MSG/kg body wt., cholinesterase (ChE) was measured at 0, 20, 40, 60, 90, 150, and 180 minutes. At 60 min., there was a drop of 30% below baseline. A significantly sharper drop was observed when prostigmine was administered simultaneously with MSG. On the other hand, control tests with histidine showed no fluctuation beyond 5%. Following infusion of ACh into a dog, the pattern of ChE activity was strikingly similar to that observed in man following MSG ingestion. Clinical response to ACh also paralleled human symptoms, except for severity. In 2 infants with Down's Syndrome, ChE chnages after MSG also followed the pattern seen in adult volunteers. Juding by this criterion infants do develop Chinese Restaurant Syndrome following MSG ingestion.