Environmental Neurotoxicology Research Project
University of South Florida, Tampa - 1997
Richard Pressinger (M. Ed.)
There has been considerable media attention given to the harmful health effects of MSG over the past several years. The Food and Drug Administration (FDA) has also come out with its recent report that MSG is "safe" for most people except for those with serious asthma difficulties.
MSG is a flavor enhancer used by the food industry for several reasons. The primary reason for its use is that it increases the "perceived" taste of any item that contains MSG. For instance, when Campbell's soup makes chicken soup, they found they would only have to add only about one-half as much chicken to their product while using MSG to achieve the same taste profile as as if they added no MSG but added twice the amount of chicken. As you can see the addition of MSG to consumer products increases the profit margin of companies that use it. Unfortunately, the use of MSG is not without consequence.
World production in 1976 was 262,000 metric tons per year. Studies by Reif-Lehrer (67 in Special Article) reported that 25% of a population sample who have been exposed to Chinese restaurant food exhibit at least some adverse symptoms.
Prior to the 1970’s, MSG was routinely added to baby food before the practice was stopped following government suggestions. Commenting on this issue, Dr. Olney, at the Department of Psychiatry, Washington University states,
According to an NAS (National Academy of
Science) Subcommittee, in considering the safety of added MSG in
baby foods, one must remember that the levels added are small - not higher
than 0.6 g%.... This means that one small jar of baby food (130 g) would
provide about 0.78 g of MSG or 0.13 g/kg of body weight for a human infant
weighing 6 kg. Based on our finding that an oral dose of 1 g/kg in the primate
or 0.5 g/kg in the mouse is sufficient to destroy hypothalamic neurons,
this leaves a 4 to 8 fold margin of safety for a human infant eating one
jar, a 2 to 4 fold margin if two jars are eaten and so forth. This is substantially
less than the 100-fold margin generally recommended to accommodate contingencies
such as species or individual differences in susceptibility to the mechanism
of a toxic compound.
In support of their assumption that human infants are invulnerable to MSG-induced brain damage, the NAS Subcommittee pointed to absence of behavioral manifestations in human infants given intravenous infusions of protein hydrolysates providing 0.3 g/kg/day of free glutamic acid. Our demonstration that MSG destroys hypothalamic neurons in monkeys as well as mice at intake doses lower than those required to produce acute behavioral manifestations points to a serious flaw in this line of reasoning. The subcutaneous injection of protein hydrolysate (0.2 cc) produces, in 10 day old infant mice, a hypothalamic lesion unaccompanied by behavior disturbances (22)."
There have been at least two other MSG studies using infant primates which found no significant brain lesions after MSG exposure (Abraham et al. (10). However, in criticism of these reports, Dr. Olney states that because of the "remarkable efficiency" with which degenerate elements are removed from the scene of MSG-induced lesion (minimal lesions are cleared from mouse brain within 12 to 18 hours), it is essential to examine the brain earlier than 24 hours (Dr. Olney’s studies examined at 3 and 5 hours). This is particularly true if, due to vomiting, the infant retained very little MSG, and therefore, sustained only a minimal lesion.
A child experiencing "innumerable seizures" at 6 months of age showed dramatic improvements after removal of MSG from the child’s diet. The case history, reported by Dr. L. Reif-Lehrer of Harvard Medical School in the journal Federal Proceedings, showed the child did not respond to dilantin treatment but had symptoms "completely alleviated by a diet that excluded exogenously added glutamate."
The child’s first seizures began at 6 months of age on October 14, 1971. For the next four months the child’s seizures continued even with treatment using dilantin, mysoline and pyridoxine. At 9 months of age the child was experiencing 100 or more seizures per day.
The following medical bibliography lists chronologically the events observed from removal of MSG from the child’s diet:
|Feb. 15, 1972||Physicians removed all MSG containing foods from the child’s diet|
|Feb. 20, 1972||(Age 10.5 mo.)||No seizures for past 3 days, first free period since onset. Reduction of anticonvulsants begun|
|March 20, 1972||(Age 11.5 mo.)||Off all anticonvulsants. No seizures.|
|May 10, 1972
||(Age 13 mo.)||Attacks 2-3 hr after surreptitious ingestion of pizza ("Snitched" from the refrigerator with the help of an older brother).|
||(Age 17 mo.)||Several attacks after ingestion of family hog, locally prepared sausage later found to contain MSG.|
||(Age 2.0 years)||No attacks for 7 months.|
||(Age 2.5 years)||Deliberate trial of a spaghetti dinner with
commercially prepared sauce containing MSG.
Seizures within 3 hours, the first one in 1 year.
||(Age 3.0 years)||Diet-watch continues. No attacks since spaghetti trial in August 1973.|
The child’s physician, Dr. M. G. Stemmermann, M.D., noted there were still no attacks as of September, 1975, except after annual test trials with an "MSG meal." Commenting on this case, Dr. Reif-Lehrer states,
"The case of the child with shudders (seizures), as well as some of the symptoms reported in a questionnaire study in our laboratory indicates a very wide spectrum of sensitivity toward MSG and suggests that perhaps some individuals should avoid exogenously added MSG. In some individuals, glutamate (or some other chemical that results from glutamate ingestion) may be getting through the blood-brain barrier, or, e.g., to certain areas of the hypothalamus, and may result in undesirable effects.... One wonders, particularly in countries where the per capita consumption of MSG is high, if there is any possibility that any subtle nervous disorders or unexplained retinal pathology could be due to cumulative effects of MSG in individuals with pre-existing abnormalities that may make them more susceptible."
Brain lesions were found in 6 rhesus infant monkeys exposed to varying levels of a single MSG dose. Researchers at the Departments of Psychiatry and Pediatrics at the Washington University School of Medicine conducted the study with rhesus monkeys because of hypotheses from other researchers stating that susceptibility to MSG induced brain damage may be limited to sub-primates (mice, rats, rabbits, etc.)
A subcommittee of nutritional experts appointed by the Food Protection Committee of the National Academy of Sciences (NAS) declared MSG to be a safe food additive requiring no regulation. The nutritional experts did admit susceptibility of infant rodents to brain damage from orally administered MSG at even the low doses of 1 gram per kilogram body weight (g/kg) but reasoned that the primate infant was most likely not at risk to MSG brain damage because it had a more mature central nervous system and more highly developed blood brain barrier at birth.
However, this theory did not hold true when tested by Dr. John Olney and colleagues at the Department of Psychiatry and Pediatrics at Washington University School of Medicine. Here, the researchers exposed 6 infant rhesus monkeys to a single MSG dose ranging from 1 to 4 g/kg and were compared to 3 control monkeys exposed in the same manner to sodium salt (table salt). The researchers found that all MSG exposed monkeys developed damage to the brain area known as the infundibular region of the hypothalamus (this corresponds to the arcuate nucleus hypothalamus area in mice).
"Our data do not support the view that only subprimates (i.e mice & rats) are susceptible to MSG-induced neurotoxicity. The lesions in our primate infants A, B and I following relatively high subcutaneous doses of MSG were so similar to those consistently observed in mice treated with high doses of MSG that it seems unrealistic to deny primate susceptibility to the MSG effect. Since lesions we detected in infants treated orally with lower doses were also similar in localization and identical in cytopathological detail to those we routinely find in infant mice treated orally with low doses of MSG, a causal link between low oral doses of MSG and necrosis (damage) of neurons in the infant primate hypothalamus also seems likely. However, since the lesions in these infants were quite small, careful consideration should be given to possible explanations other than MSG toxicity."
To determine at what level the food additives MSG and Aspartate could cause brain lesions, it was given to a group of 75 infant mice starting at the very low "normal human exposure levels" of .25-.50 g/kg (grams of MSG per kilogram of animal body weight) upwards to 2 g/kg. In each case only a single dose of the compound was given. Five hours after MSG and Aspartate treatment each animal was anaesthetized and examinations were performed on the brain cells within the hypothalamus using a light microscope. The results showed that only the very lowest .25 g/kg level had no harmful observable effect upon the brain cells. Of the twenty-three animals given .5 g/kg doses of MSG, twelve (52%) suffered hypothalamic damage; and of sixteen animals treated at .75 g/kg, thirteen (81%) were affected. Nineteen animals (100%) treated at 1g/kg and seven (100%) treated with 2 g/kg developed lesions in the part of the hypothalamus known as the arcuate nucleus.
photograph at left shows normal brain area called the arcuate nucleus.
Photograph at right shows same area after exposure to MSG at 1 g/kg.
White areas are dead brain cells resulting from the MSG exposure.
It was found that MSG and Aspartate can combine their damage potential when test animals were fed 0.5 g/kg of each compound simultaneously that they developed the amount of hypothalamic damage characteristically seen in animals treated with either agent at 1 g/kg.
To investigate the possibility of long term effects from MSG ingestion, Dr. Olney followed five litters of Swiss albino mice, consisting of 38 healthy animals, from birth to nine months of age. Twenty animals received injections of MSG daily from 1 to 10 days after birth, 18 control animals received no treatment.
The results showed MSG treated animals appeared stunted in growth and still remained shorter than controls on day 30. Of significant interest, animals treated with MSG continued to gain weight on unrestricted diets beyond the age of 5 months. Average weights of the 5 month old animals were 37 grams for the non-MSG treated and 57 grams for the MSG treated animals (see picture at right). It is important to point out that contrary to expectation, the "obese" MSG treated animals actually consumed less food than their thinner control counterparts, implying damage to the brain area responsible for controlling body weight. Mean per capita food consumption over the daily 4 hour measuring period was 2.5 grams for the controls and 1.7 grams for the MSG treated animals.
Also noted at 5 months, the MSG animals were quite lethargic as adults, and they lacked the sleekness of body coat seen in the controls. The reproductive capacity of the MSG females was also modified in that they repeatedly failed to conceive in spite of adequate exposure from 5 to 9 months of age.
In summary, Dr. Olney writes,
"These observations, linking MSG treatment of the neonatal mouse with a syndrome of manifestations, including skeletal stunting, marked adiposity, and sterility of the female, coupled with histopathological findings in several organs associated with endocrine function, suggest a complex endocrine disturbance. In view of the additional finding of lesions in regions of the brain thought to function as neuroendocrine regulatory centers, a unitary hypothesis might be constructed relating all or most of the findings to the neonatal disruptions of neuronal development in these centers.... The assumption that MSG is an entirely innocuous substance for human consumption has been questioned recently in view of its role in the Chines Restaurant syndrome. The finding that neuronal necrosis can be induced in the immature mouse brain by 0.5 mg/kg of MSG raises the more specific question whether there is any risk to the developing human nervous system by maternal use of MSG during pregnancy. The primate placenta maintains amino acids in consistently higher concentrations in the fetal circulation than those found in the maternal circulation, the ratio of glutamic acid being grater than 2:1. In fact, when high doses of phenylalanine were given to a pregnant rhesus monkey, the ratio of mother to fetus for this amino acid remained unchanged so that exceedingly high fetal blood levels resulted. The possibility that brain lesions could occur in the developing primate embryo in response to increased glutamic acid concentrations in the maternal circulation, therefore, warrants investigation."
Aspartame is an artificial sweetener that has developed widespread use in the United States. The compound was originally given FDA approval in 1974, however, its purported safety was called into question and approval was suspended pending further investigation. In fact, final approval for consumer use was not finally given until the mid 1980’s.
As with MSG, researchers Reynolds, Butler and Lemkey-Johnson (Journal of Toxicology and Environmental Health, 2: 471-480, 1976) reported that 0.5 or 1.0 g/kg of aspartame on Days 6-12 resulted in small hypothalamic lesions in neonatal mice. These results and the potentially wide use of a new artificial sweetener suggested a need for further examination of the neurobehavioral consequences of aspartame administration. Interest in and concern about aspartame has been elevated by the fact that its metabolic breakdown will liberate the amino acids phenylalanine and aspartate.