Wednesday, March 20, 2013


MSG is my issue.  MSG: the toxic cousin of toxic aspartame.  But when the greedy dairy industry proposed to hide aspartame more deeply in “flavored milk” -- not just use aspartame in "flavored milk" -- it was more than I could stomach. 

If you’ve been following the Truth in Labeling Campaign, you know that Jack Samuels had a life-threatening sensitivity of processed free glutamic acid (MSG).  Searching for insight into his problem, he found that the glutamic acid portion of monosodium glutamate kills brain cells in the area of the hypothalamus and causes subsequent endocrine disorders;[1] and he found that aspartic acid, a second neurotoxic amino acid, does exactly the same.[2] 

Over time, Jack found out more about the aspartic acid in aspartame.  Glutamic acid and aspartic acid are structural analogs, they cause the same brain damage in the same regions of the brain, and both are endocrine disruptors.  Subsequently Jack found that with a single exception[3], MSG and aspartame cause the same adverse reactions.[4],[5] 

There is something else you should know about the relationship between glutamic acid and aspartic acid.  What researchers found to be true of glutamic acid was also true of aspartic acid.  They load on the same receptors in the brain and nervous system and cause the same adverse reactions; and since glutamic acid was easier to work with,[6] relatively little research on the toxic effects of aspartic acid per se was done.  Thus when you hear from the aspartame industry (which in my thinking includes the FDA) that there is very little research pointing to the toxic potential of aspartic acid or aspartame, you need to realize that the abundance of research that points to the toxic potential of glutamic acid also points to the toxic potential of aspartic acid and aspartame.

In the blogs that follow, you will find the proposal of the dairy industry to change the standard of identify for “flavored milk” to better hide the use of aspartame from consumers.

In the second blog, we outline the sordid history of aspartame’s approval for use in food. 

In the third blog, we present data that demonstrate that the aspartic acid in aspartame, and aspartame itself, have toxic potential; and we take the opportunity to tell you how Ajinomoto’s International Glutamate Technical Committee used aspartame-laced placebos in their double-blind studies on the safety of monosodium glutamate. 


[2] Kizer JS, Nemeroff CB, Youngblood WW. Neurotoxic amino acids and structurally related analogs. Pharmacological Reviews. 1978;29(4):301-318.
Olney JW. Brain damage and oral intake of certain amino acids. In: Transport Phenomena in the Nervous System: Physiological and Pathological Aspects. Levi G, Battistin L, Lajtha A, Eds. New York: Plenum Press, 1976.
also: Advances in Experimental Medicine and Biology. 1976;69:497-506.
Olney JW, Ho OL. Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine.  Nature. 1970;227:609-611.
Olney JW, Ho OL, Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system.  Exp Brain Res. 1971;14:61-67.
[3] One eyed blindness, possibly caused by the methanol in aspartame
[6] Olney JW.  Personal communication

Sunday, November 13, 2011

Cancer: MSG and Cancer

The message
There is evidence that suggests that MSG produced by any method causes or exacerbates cancer(1).  At the same time, there is undeniable evidence that MSG manufactured using acid hydrolysis  always contains carcinogenic mono and dichloro propanols(2-5) and that MSG produced when a Maillard reaction occurs, always contains carcinogenic heterocyclic amines(6).

It is just that simple.  Ingredients/products that contain acid hydrolyzed proteins and ingredients/products that contain reaction flavors contain carcinogens.  Much of the processed food in the United States contains carcinogenic acid hydrolyzed proteins.  The U.S. Food and Drug Administration (FDA) has been aware of the relationship between MSG and cancer since the early 1990s (4).  The European Union is equally aware(5).    

The background
Truly natural glutamic acid -- as it exists in its unadulterated form in nature -- is an acidic amino acid.  It is found in abundance in both plant and animal protein where it is bound (tied) to other amino acids in chains. 
Manufactured glutamic acid (MSG) is different.  It is produced commercially in manufacturing and/or chemical plants, and/or by fermentation.
There are five basic methods presently used to produce most MSG.  Each of these methods produces glutamic acid that stands alone, i.e, glutamic acid that is no longer tied to other amino acids. Each generates a product of human invention for which it is possible to obtain a patent. 
All processed free glutamic acid (MSG) – no matter how produced -- is neurotoxic (kills brain cells) and is endocrine disrupting (damages the endocrine system) (7-8).  In addition, all processed free glutamic acid (MSG) will cause adverse reactions ranging from feelings of mild discomfort or simple skin rash to such things as irritable bowel, asthma, migraine headache, mood swings, heart irregularities, asthma, seizures, and depression when the amount of MSG ingested exceeds a person's MSG-tolerance level(9).
All processed free glutamic acid (MSG), no matter how produced, is accompanied by unwanted by-products of production referred to as impurities.  Impurities are invariably produced by all methods used for breaking down protein (autolysis, enzymolysis, and acid hydrolysis)(2,6,10-15); by all methods used to produce monosodium glutamate; and by all methods use to produce reaction or processed flavors(6,10).  Only the impurities associated with the MSG produced by acid hydrolysis and the Maillard reaction include cancer-causing substances.

How do we know what we know?   We know from the paper Regulatory status of maillard reactions flavors that Lawrence Lin presented in August 1992 at a meeting of the American Chemical Society(10).  We know from the National Toxicology Program (NTP) of the National Institute of Environmental Health Sciences (NIEHS) at the National Institutes of Health (NIH) Review of Toxicological Literature(4).  And we know from the Codex Alimentarius Commission Position Paper on Chloropropanols(5).


[1]. Blaylock R. (ed). Blaylock Wellness Report.  The Great Cancer Lie: It is Preventable and Beatable.  October, 2008.
[2]. Pommer K. New Proteoloytic enzymes for the production of savory ingredients. Cereal Foods World.1995;40(10):745-748.

[3]. Food Chemical News, Dec 2, 1996. p24-25.
[4]. National Toxicology Program, National Institute of Environmental Health Sciences, US Department of Health and Human Services.  Masten  Review of toxicological literature. SA Project Officer. Research Triangle Park, North Carolina, January 2005 accessed 4.21.2011.
[5]. Codex Alimentarius Commission, World Health Organization.  Joint FAO/WHO food standards programme, codex committee on food additives and contaminants, Thirty-third Session,   The Hague, March 12-16, 2001. ( accessed 4/21/2011.
[6]. Food Chemical News, May 31, 1993. p16.
[7]. Olney JW, Ho OL, Rhee V. Brain-damaging potential of protein hydrolysates. N Engl J Med. 1973;289:391-393.

[10]. Lin LJ. Regulatory status of maillard reactions flavors, Washington DC: Division of Food and Color Additives, Center for Food Safety and Applied Nutrition, Food and Drug Administration. Paper presented at a meeting of the American Chemical Society, August 24, 1992.
[11]. Man EH, Bada JL. Dietary D-Amino Acids. Ann Rev Nutr.1987;7:209-225.

[12]. Konno R, Oowada T, Ozaki A, Iida T, Niwa A, Yasumura Y, Mizutani T. Origin of D-alanine present in urine of mutant mice lacking D-amino-acid oxidase activity. Am J Physiol. 1993;265:G699-G703.
[13]. Sjostrom LB. Flavor potentiators. In: Furia TE, CRC Handbook of Food Additives. Cleveland: CRC Press, 1972: 513-521.
[14]. Rundlett KL, Armstrong DW. Evaluation of free D-glutamate in processed foods. Chirality. 1994;6:277-282.

[15]. Food Chemical News, Dec 2, 1996. p24-25.

[16]. Deki M, Echizen A, Temma T. Minor components in monosodium glutamate. Kanzei Chuo Bunsekishoho.1977;17:59-62.


Hydrolyzed Vegetable Proteins: The Full Story. Author: Jack L. Samuels

Saturday, May 14, 2011

Evidence of Monosodium Glutamate-induced Brain Damage and Endocrine Disorders


In the late 60s, Olney became suspicious that obesity in mice might be associated with hypothalamic lesions caused by monosodium glutamate treatment.  In 1969, he first reported that monosodium glutamate treatment did indeed cause brain lesions in experimental animals; and that the monosodium glutamate-induced brain lesions were followed by reproductive disorders, gross obesity, and other endocrine disorders.

Research that followed into the 1970s fell into two categories.  The first confirmed Olney’s findings.  The second, using methodology which precluded the identification of brain lesions, produced negative results from which glutamate-industry researchers would conclude that their failure to demonstrate monosodium glutamate-induced brain lesions demonstrated that monosodium glutamate-induced brain lesions do not exist.

Today, the toxic effects of glutamic acid on certain brain cells are so well understood that researchers interested in brain function and development of pharmaceuticals that might block the effects of glutamic acid, often use glutamic acid as an ablative tool to kill selected brain cells.

Following is a review of research that demonstrates that monosodium glutamate treatment causes brain lesions and neuroendocrine disorders in laboratory animals.

Lesions in the arcuate nucleus of the hypothalamus of neonatal and infant animals.

In the late 60s, Olney(59) became suspicious that obesity in mice, which was observed after neonatal mice were treated with monosodium glutamate for purposes of inducing and studying retinal pathology, might be associated with hypothalamic lesions caused by monosodium glutamate treatment; and in 1969, he first reported that monosodium glutamate treatment caused brain lesions, particularly acute neuronal necrosis in several regions of the developing brain of neonatal mice, and acute lesions in the brains of adult mice given 5 to 7 mg/g of glutamate subcutaneously(59).

Research that followed confirmed that monosodium glutamate, which was routinely given as the sodium salt, monosodium glutamate (brand name Accent), induces hypothalamic damage when given to immature animals after either subcutaneous (60,61,62,63,64,66,67,68,69,70,71,72,73,74,75,76,77,78,81) or oral(67,73,74,76,82,83,84,85,86) doses.

Work by Lemkey-Johnston and Reynolds(86) published in 1974 included an extensive review of the data on brain lesions in mice. They confirmed the phenomenon of monosodium glutamate induced neurotoxicity; described the sequence of the lesions; and emphasized the critical aspects of species variation, developmental age, route of administration, time of examination of brain material after insult, and thoroughness of tissue sampling methods. A review of monosodium glutamate induced neurotoxicity, published by Olney in 1976(87), mentioned species (immature mice, rats, rabbits, guinea pigs, chicks, and rhesus monkeys) demonstrating monosodium glutamate induced neurotoxicity, and the efficiency of both oral and subcutaneous administration of monosodium glutamate in producing acute neuronal necrosis; discussed the nature and extent of the damage done by monosodium glutamate administration and the impact of monosodium glutamate administration to monosodium glutamate levels in both brain and blood; and discussed the similar neurotoxic effects of a variety of acidic structural analogues.

Studies of sub-human primates were thought to be particularly meaningful because monosodium glutamate toxicity found in sub-human primates might be relevant to humans. As early as 1969, Olney(61) had suggested that monosodium glutamate could be involved in the unexplained brain damage syndromes occurring in the course of human ontogenesis. Olney(61) demonstrated that the infant rhesus monkey (Macaca mulatta) is susceptible to monosodium glutamate-induced brain damage when administered a high dose (2.7g monosodium glutamate/kg of body weight) subcutaneously.

Olney et al.(74) expanded Olney's earlier work with a study of eight additional infant rhesus monkeys and, using light microscopy and the electron microscope, reconfirmed Olney's earlier findings of hypothalamic lesions, and discussed the findings of both Abraham et al.(75) and Reynolds et al.(88) who had questioned his work. Olney found his data to be entirely consistent with studies done previously by his own and other laboratories on all species of animals tested.

Neuroendocrine disorders

Olney found not only hypothalamic lesions in 1969, but described stunted skeletal development, obesity, and female sterility, as well as a spate of observed pathological changes found in several brain regions associated with endocrine function in maturing mice which had been given monosodium glutamate as neonates(59).

Longitudinal studies in which neonatal/infant animals were given doses of monosodium glutamate and then observed over a period of time before being sacrificed for brain examination, repeatedly supported Olney's early findings of abnormal development, behavioral aberration, and neuroendocrine disorder. Animals treated with monosodium glutamate as neonates or in the first 12 days of life were shown to suffer neuroendocrine disturbances including obesity and stunting, abnormalities of the reproductive system, and underdevelopment of certain endocrine glands (59,68,70,86,88,89,90,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106) and possible learning deficits either immediately or in later life (92,95, 96,107,108,109,110,112,113). In addition, there were reports of behavioral reactions including somnolence and seizures (114,115,116,117,119,120,121); tail automutilation (94,108); and learned taste aversion(110).  Irritability to touch was interpreted as conspicuous emotional change by Nemeroff(94). Lynch(122) reported hyperglycemia along with growth suppression. He noted that hyperglycemia did not occur when subjects were given intact protein containing a large amount of glutamate.

Olney et al.(123,124,125) have written a number of review articles which summarize the data on neuroendocrine dysfunction following monosodium glutamate treatment. Nemeroff(126) has written another.

Ad libitum feeding studies

At the time, a seemingly logical first step was to study the effects of monosodium glutamate on subhuman primates; and, as already noted, hypothalamic lesions had been demonstrated in monkeys as early as 1969(61). A seemingly logical second step was to study "normal" ingestion of monosodium glutamate as opposed to some kind of forced feeding. Many felt that ad libitum feeding of laboratory animals parallels the human situation more closely than either subcutaneous or gavage administration of monosodium glutamate, and that ad libitum feeding studies were, therefore, the vehicle of choice. Ad libitum feeding would give animals free access to feed or water, thereby allowing the animals to self-regulate intake. Some tended to disagree, feeling that the ad libitum feeding studies were, by and large, studies that had the greatest potential for minimizing the amount of monosodium glutamate actually ingested while registering the irrelevant amount of monosodium glutamate available.

Two studies that demonstrate neurotoxic reactions after ad libitum feeding of monosodium glutamate are reported here. In a 1979 study done as part of a project designed to evaluate a developmental test battery for neurobehavioral toxicity in rats, in which rats were exposed to monosodium glutamate and other food additives mixed with ground Purina rat chow beginning five days after arrival at the laboratory(109), it was demonstrated that high doses of dietary monosodium glutamate produce behavioral variations. Monosodium glutamate was mixed with food as opposed to being administered subcutaneously or by gavage. A year later, dietary studies demonstrated that weanling mice will voluntarily ingest monosodium glutamate and that such voluntary ingestion results in readily detectable brain damage(127). 

Focus on older animals

Most studies demonstrating retinal necrosis, brain lesions and/or neuroendocrine dysfunction, focused on neonatal or infant animals. Researchers were primarily interested in producing lesions in order to expand their knowledge of brain function; and lesions were most easily produced in the young. It was, however, also of scientific interest to understand the relationship of age of animal to type and severity of lesion or dysfunction. Thus, older animals were studied, but not to the same extent as the young.

Hypothalamic lesions have been produced in adult animals using considerably greater doses of monosodium glutamate than those required to produce lesions in younger animals. Nemeroff(126) reported that the least effective dose for a ten day old mouse, given orally, is .5g/kg of body weight, and given subcutaneously is .35g/kg of body weight. According to Olney(128), the dose required to damage the adult rodent brain is given as 1.5-2 mg/g of body weight as compared to 0.3-0.5mg/g required to damage the brain of an infant rodent. Only minimal damage is induced unless very high doses (4-8 mg/g) are used(123).

Although advances in technology have facilitated the observation of brain lesions to some extent, it is still true today, as it was in the 1960s, that simple light microscopes are adequate to identifying monosodium glutamate induced lesions if one looks in sensitive locations within 4-5 hours of monosodium glutamate administration. By 24 hours after insult, lesions will be filled in ("healed") with cells other than neurons. Thus the "hole" is filled in, but lost neurons are not replaced. The damage will have been done, but will be virtually impossible to see. Although it is now possible under optimal circumstances to count neurons in well defined areas, the arcuate nucleus of the hypothalamus is not a well defined area, and lesions in that area will defy detection after as little as 24 hours after monosodium glutamate administration. One could not, therefore, ascertain whether or not an adult animal given monosodium glutamate as an infant, had suffered a lesion in the arcuate nucleus.

Industry’s response – refuted by independent researchers

Not all studies reported brain damage following administration or ingestion of monosodium glutamate. Adamo and Ratner(131) and Oser et al.(132) failed to reproduce findings of neurotoxicity affecting the brains of non-primates. Adamo and Ratner(131) used rats, not mice as Olney(59) had, but maintained that otherwise the experimental approach used was "very similar." Oser et al.(132) studied mice, rats, and beagles (dogs). Although their methodology varied considerably from Olney's, they concluded that they could "...offer no explanation for the fact that [their] not confirm those of Olney...."  

Arees and Mayer(64) reproduced Olney's(56,59,61) findings only in part. Their discussion focused more on the question of human consumption of monosodium glutamate as food than on reasons for differences between the various studies.

All three of these negative studies were refuted by both Olney(60,133) and Burde(73) who independently reviewed the literature and found that these early discrepancies could be attributed to: 1) failure on the part of investigators to attempt to replicate Olney's methods; and 2) use by investigators of entirely different (and inappropriate) methods of preservation and staining of brain tissue in the analysis of results.

Burde(73) speculated that the method of fixation and staining used by Adamo and Ratner(131) obscured the existence of the lesion, and noted that their dose schedule was not appropriate; that Oser et al.(132) used a minimal effective dose and did not examine the rats and mice until 24 hours after insult, even though it was known that by 24 hours after insult with a minimal dose such as the one used by Oser, all signs of edema would have disappeared, and necrotic cells would already have been phagocytized. Burde found the interpretation by Arees and Mayer(64), that the lesion produced by monosodium glutamate is limited to "microglia," to be puzzling, particularly in light of the fact that most of the cells of the arcuate nucleus are known to be small neurons. Furthermore, using Olney's exact methods, Burde(73) replicated Olney's previous findings.

Olney's(60) review of the discrepancies, pointed out that the failure of Oser et al.(132) to detect brain damage in any of the three species they studied might be accounted for by their having limited the monosodium glutamate dose to a single, minimally effective dosage; failure to use a feeding tube to assure that the full dose was received by orally treated animals; failure to examine brains in appropriate post treatment intervals (which are particularly relevant in cases of minimal effective dosage); and use of relatively unrefined techniques for tissue preparation.

Olney(60) also noted that in a 1971 study of MSG-induced optic pathway lesions in infant mice following subcutaneous injection, Arees et al. had demonstrated that neuronal degeneration does occur in the infant mouse brain following subcutaneous treatment with monosodium glutamate. Thus the discrepancies noted by Arees and Mayer in 1970(64) became resolved.

Finally, Olney(60,133) suggested that methodological variables might well explain the failure of Adamo and Ratner(131) to demonstrate lesions in the rat.

The subject of tissue preparation has been addressed by a number of people. Takasaki(69) stated it clearly: "...changes disappeared at least 24...[hours] after injection....The results should be borne in mind when histological examination is performed on changes of the hypothalamus caused by administration with MSG. It is [especially] so in animals administered with a small dose of MSG, because necrotic neurons are few and the glial reaction that occurs secondarily is very mild in the AN [arcuate nucleus]. Without punctual preparation after administration, the effect upon the hypothalamus is apt to be overlooked in these animals"(69).

Olney(67,81,133,134) and Murakami(135) have discussed the problem in similar terms. Olney(67) has discussed such methodological problems in great detail.

In 1973, Filer and Stegink(136) published an editorial in the New England Journal of Medicine that suggested that the neurotoxic effects of monosodium glutamate and its related amino acids, aspartate and cysteine, in species other than the mouse, are debatable. In turn, Olney et al.(137) pointed out that neurotoxic effects of monosodium glutamate and its related amino acids had been well documented, and that the "null effect" reported by Filer and Stegink was a function of faulty methodology, not strain specificity--a fact which had been pointed out earlier by Burde(71,74). Olney noted that Filer and Stegink supported their argument by pointing out that no neurotoxic effects of monosodium glutamate had been reported in the guinea pig, which was, at the time, an unstudied species. Olney further reviewed the criticisms of his own research proffered by Filer and Stegink and suggested that a more careful reading of the research as presented would resolve their concerns.

There were other studies that failed to confirm toxic effects of monosodium glutamate, and there were criticisms of Olney's work. Abraham(75), mentioned earlier, found toxic effects when monosodium glutamate administration was subcutaneous, but very little when administration was oral.

Lowe(138) criticized Olney(61) for failure to provide data on plasma monosodium glutamate concentrations, and for lack of a control in his single infant monkey study. Zavon(139) criticized Olney for lack of a control animal and for lack of detail in reporting the same study. Olney(140) responded to both Lowe and Zavon with detail gathered from mouse studies and an apology that he had had only the one monkey available at the time of his study. Blood et al. (141) criticized Olney (59) for questioning the safety of monosodium glutamate after parenteral, as opposed to oral, administration; failure to clearly elucidate his methodology; and use of doses which far exceeded Blood et al.'s estimate of "...the total daily intake [of glutamate] from all reasonably possible uses... (.7 g per day) in an average adult"(141).

Olney(142), in reply to Blood et al.(141), provided the figures requested, and suggested that to truly establish the safety of monosodium glutamate if, indeed, that could be done, solid research was needed.

Two studies took exception to Olney's finding of hypothalamic lesion in sub-human primates due to loading of monosodium glutamate. Abraham et al.(75) treated four monkeys and failed to reproduce the findings of Olney and Sharpe(61). Reynolds et al.(88,144) treated 16 sub-human primates which were compared to five controls. They, too, failed to reproduce the findings of Olney and Sharpe(61), and found, instead, a "spectrum of degenerative changes" which they attributed to inadequate fixation procedures rather than to the effects of monosodium glutamate.

Olney(74) noted that elements of the research design and methodology of Abraham et al.(75) and Reynolds et al.(88,139,140) distinguished their study from his.  Reynolds et al. used only a spot sampling technique when two of the rhesus infants, each treated with low oral doses of monosodium glutamate, were examined by electron microscopy, so the possible occurrence of small lesions in these brains was not actually ruled out. In addition, the method used for preparation of brains for examination by light microscopy has been found unsatisfactory for evaluating even large monosodium glutamate-induced lesions in infant rodent brains; and subsequent information provided by Reynolds indicated that some of the infant monkeys vomited an unknown portion of the administered dose.

Abraham et al.(75) supported their findings with a single light micrograph from a rhesus infant sacrificed 24 hours following oral intake of an emetic dose (4 g/kg of body weight) of monosodium glutamate, although four monkeys were studied. Moreover, little or no evidence of lesion would be expected 24 hours after monosodium glutamate insult because damaged elements are removed from the scene of an monosodium glutamate-induced lesion with such remarkable efficiency, that 24 hours after insult, without pre- and post-insult comparison, it is virtually impossible to determine if damage has been done. In general, Abraham's work appears to be vulnerable to the criticism that he maintains that he is replicating work done by Olney, but does not do so. A careful comparison of the two studies will demonstrate that age of subject, dosage administered, time between insult and examination of tissue, and methods of tissue preparation all differ. Abraham's study can also be criticized for use of methodology known to be inappropriate for identifying monosodium glutamate lesions.  Finally, it was also noted by Nemeroff(126) that Abraham  et al.(75) found in both control and monosodium glutamate treated monkeys a "very small proportion of necrotic or damaged neuronal cells and the arcuate nuclear region of the hypothalamus." One might suspect that this might happen if the placebo, as well as the test material, contained small amounts of an excitotoxin identical, or similar to, monosodium glutamate.

Also failing to reproduce neurotoxicity in primates, were studies of Abraham et al.(145), Newman et al.(146), and Stegink et al.(147). Stegink et al.(147) used the same data as Reynolds et al.(88,139,140) with two additional monkeys, and used the same methodology for tissue staining.  His work, then, is subject to the same criticisms as hers. Abraham et al. stated that their present investigation was undertaken in an attempt to resolve some aspects of the controversy. However, the details of this methodology were identical to those of their earlier study(75) and are subject to the same criticisms.

Newman et al.(146) found " evidence in any instance of any change that could be attributed to MSG as described by Olney and Sharpe, although there were artifacts in some inadequately fixed areas as recorded by Reynolds and her co-workers."  The initial study was carried out with animals of 108, 99, 60, and 3 days, with unspecified histories. Information pertaining to the animals is incomplete. Their history is uncertain. There is no information pertaining to the first 108 days of an animal's life. Quoting from the research report: "Rhesus monkeys were maintained and observed in the primate buildings of HRC, where most of them were bred."  "The test solution was readily consumed voluntarily by all animals on all occasions throughout the study;" "The 3-day-old monkey had a few hypochromatic nuclei, and a minimal degree of vacuolation in the ventral hypothalamus, but these findings were not regarded as significant." "By electron microscopy, changes of the type reported by Olney and Sharpe were seen in both test and control animals, and were attributed to fixation artefact."  (Emphasis added.)

In a 1976 study by Reynolds et al.(148) which produced negative results relative to abnormalities of the subinfundibular region of the monkey brain, both mice and monkeys were studied. Mice, but not monkeys, were reported to show brain lesions. The monkeys were infant macaques with age ranging between 30 minutes and 14 days. It is of interest (and concern) to note that the cross section presented in Figure 4 of "...a 7-day-old infant Macaca fascicularis monkey that ingested 4 g/kg monosodium glutamate..." appears, in every aspect, to be identical to a section of an "...infant rhesus monkey which received 4 g/kg of monosodium glutamate by stomach tube..." presented in Figure 3 of the report by Stegink et al.(147). The monosodium glutamate in Reynolds et al. study was prepared as a 20% w/v solution in water and administered as a single dose of as much as 4 g/kg monosodium glutamate. It was reported that monkeys received various doses, but dosage by age was not given. The techniques for evaluation of mouse brains were the same as those used by Lemkey-Johnston and Reynolds(86) and Reynolds et al.(88) in previously reported studies. These had been found by Olney(74) to be inappropriate. No information is given about the timing involved or the techniques used for evaluation of monkey brains.  Reynolds concludes, "Neither aspartame nor MSG is capable of eliciting a lesion in the neonatal monkey brain." (Emphasis added.)

In failing to replicate Olney's methods, researchers used entirely different (and inappropriate) methods of preservation and staining of brain tissue in analysis of results; limited the monosodium glutamate dose to a single, minimally effective dosage; failed to use a feeding tube to assure that the full dose was received by orally treated animals; and/or failed to examine brains in appropriate post treatment intervals (which are particularly relevant in cases of minimal effective dosage).

Delay in examination of potentially damaged tissue beyond the time that the damage could be observed was common to these studies.  Delay in administering or feeding monosodium glutamate to test animals beyond the age that brain damage would most readily be inflicted, would be similarly effective for obscuring the negative effects of monosodium glutamate treatment.

A number of the negative studies were ad libitum studies.  Ad libitum feeding gives animals free access to feed or water, allowing animals to self-regulate intake, and, therefore, would appear to closely approximate the human condition.  At the same time, the amount of monosodium glutamate actually ingested could be minimized while the amount of monosodium glutamate available (but not necessarily ingested) was reported. Olney(127) pointed out that ad libitum animal studies fall far short of approximating the human condition.

Negative results could also be assured if researchers considered the effect of monosodium glutamate on irrelevant variables, i.e., variables that had never been shown to be associated with monosodium glutamate-induced toxicity. Blood pressure and weight loss are examples. A variation used in human studies of adverse reactions (as distinct from brain lesions) would be study of effects of  ingestion of monosodium glutamate on plasma glutamate level.  Elevated plasma glutamate has been shown to be associated with production of brain lesions, but has never been shown to be relevant to monosodium glutamate-induced adverse reactions. The logical fallacy in these studies comes when it is concluded that finding nothing while studying irrelevant variables proves that monosodium glutamate is safe.

A number of studies used non-relevant levels of otherwise relevant variables. Since females exhibit reproductive disorders and males do not, males, but not females, might be studied. Similarly, if a particular neuroendocrine change would not exhibit itself in less than 20 days following insult with monosodium glutamate, researchers would examine test animals after 15 days.

A number of studies drew conclusions not warranted by their data. Matsuzawa et al.(99) did a series of studies using both neonatal and 10 day old rats, given oral and subcutaneous doses of monosodium glutamate at a total of 4 different doses. Controls were given saline solution. The ad libitum diet was given "...for 10 days after weaning (at 20 days)." By 1979, the date of the study, it was well understood that the timing used was outside of the range of the animal's most susceptible age. Based on this methodology Matsuzawa concluded that "MSG therefore produces marked reproductive endocrine abnormalities after maturation only when injected parenterally early in postnatal life, in repeated, very large doses. The development of reproductive endocrine function is not affected by MSG unless neurological damage occurs in the hypothalamus by any route of administration." (Emphasis added.)

The identical approach was taken by Takasaki et al.(98). They report that, "Adverse effects from MSG have never been reported from dietary administration." (Emphasis added.) In this case, "never" equals four studies. They concluded that "MSG does not exert an adverse effect on somatic growth in that the hypothalamic neurons are not injured by any routes of administration, and the MSG did not induce somatic deficiency under the conditions of our experiments, which mimic the intended conditions of use of this material as a food additive."

Conclusions drawn from these studies are based on negative results.  Using inferential statistics, the question raised is whether or not a difference found between two groups of subjects or two sets of measurements could have occurred by chance. If statistical analysis determines that observed differences would rarely have occurred by chance, the investigator would describe those differences as statistically significant, and would specify the probability with which differences of that magnitude would be expected to be reproduced if the experiment were replicated at another time.  In statistical parlance, we would say that the investigator had tested the hypothesis that there would be no difference between two groups (the “null hypothesis”), and had rejected that hypothesis when he found that there was, indeed, a significant difference.  The statistical model on which these statistics are based allows the investigator to conclude that it is highly likely (the probability being 95 percent or 99 percent) that differences found were not due to chance.  The statistical model does not allow the investigator to conclude that there is no difference between the two groups when a statistically significant difference is not found.

The following examples illustrate the reasoning.

.....Example 1: Suppose it is known unequivocally from space missions that there is life on Mars, and that all Martians (group 1) have 2 heads.  On Thursday an alien spacecraft lands in your back yard, and several aliens emerge (group 2).  If the visiting aliens had three heads, we would know that the three-headed aliens were not from Mars, and that there must be life on other planets.  (There is clearly a difference between the two groups of aliens.)   However if the visiting aliens had two heads (just like the Martians), they might be from Mars, or they might come from another planet. Perhaps there are 2-headed aliens on another planet.

.....Example 2: Suppose that subjects are given purple dye number 12 or a placebo, and that the numbers of headaches reported by each group are the same.  If reports of headache had been significantly greater in the group given purple dye, we could have concluded, with a certain amount of confidence, that purple dye caused headaches.  But since reports of headaches were approximately the same for both groups, we would not know what to conclude.  It might be that purple dye does not cause headaches.  It might have been that subjects were eating something with purple dye in it during the studies, giving the placebo group headaches; or that purple dye only causes headaches in females and all of the subjects were males.

Drawing conclusions based on failure to find a difference (i.e., on failure to reject the null hypothesis) is grossly inappropriate(149,150,151). Given the statistical model, rigorous demonstration of the truth of the null hypothesis (that there is no difference between groups) is a logical impossibility(149).

In their 1979 summary of monosodium glutamate toxicity in laboratory animals, Heywood and Worden(152) cite nine chronic animal studies in which various species were given ad libitum feedings of monosodium glutamate over extended periods of time. These include studies by Ebert(153), Owen et al.(154,155), Semprini et al.(156), and Wen et al.(157). Because we have no data on chronic animal studies from persons other than those who have produced negative studies, and, therefore, have no records of positive results, we have no basis for evaluating the levels of variables used in these studies. And because they are incomplete and imprecise in detailing their methodology, it is difficult to evaluate the research, as a whole. Ebert(153,158) apparently used data from a 1953 study done at Arthur D. Little, Inc. entitled, "Report on a study of L-monosodium glutamate, DL monosodium glutamate and L glutamic acid with respect to potential carcinogenicity."  His mice were clearly older than Olney's mice(87). The 1970 report of these data(153) was in the form of an abstract. The 1979 reports(158,159) were expanded abstracts done, " comply with the suggestion of the Select Committee on GRAS Substances during hearings on glutamates, held at Bethesda, Maryland on July 25-27, 1977"(158). We know that these studies producing negative results and thereupon claiming to "prove" that monosodium glutamate is a safe food additive, are subject to the limitations of the statistics that they use, and that from the point of view of the statistical model, any conclusion of safety based on failure to find a difference between two groups is invalid. We also know that the procedures of Wen et al.(157) are subject to the same criticisms(60,73,133) as studies by Adamo and Ratner(131).

In another 1979 summary of results of dietary administration of monosodium glutamate, Anantharaman(160) stated that studies indicated that "...dietary administration of MSG at even very high doses was not found to result in any of these symptoms [produced by other routes of administration], including the endocrine disturbances." They cited Huang(161), Wen(157), Takasaki(162), Bunyan(163), Owen(154), and Trentini(105). They also cited two year rat studies by Ebert(153) and Owen et al.(154), where no abnormalities were found in successive generations. And in their own study(160), they also produced negative results.

Studies by Owen(154), Takasaki(162), and Wen(157) have already been discussed in some detail. The additional studies mentioned here are subject to previously discussed statistical limitations.

The study reported by Anantharaman(160) must be criticized on additional grounds. Unlike most of the research reported, Anantharaman provides a great deal of detail, including detail of the exact nature of the basal diet provided. And in that basal diet we note that "yeast food" is listed as a component of the protein (page 236, Table 3). When we checked in 1990, yeast food invariably contained either protease (which creates MSG, the toxic component of monosodium glutamate, during manufacture) or L-cysteine which produces neurotoxic effects somewhat different from, but more extensive than, the effects of monosodium glutamate. We are suspicious, then, that the failure to find differences in growth of control and experimental groups may be due to the fact that both groups were receiving neurotoxic substances in their basal diet.

Using inappropriate placebo materials in human studies has been discussed by others. In 1981, Rippere(164) criticized the use of common food allergens as placebo materials, noting that even a minute trace of an allergen might trigger severe symptoms in a sensitized individual. In a study by Abraham et at.(145) cited earlier, it was noted that the control group exhibited some small evidence of brain damage just as the experimental group did, raising a question of what placebo materials might have been used there. In 1990, this author questioned research done by Goldschmiedt, Redfern, and Feldman(165) which used beef broth as a placebo for controls. In the United States, one cannot purchase commercially prepared beef broth that does not contain some MSG-containing ingredient (hydrolyzed protein, yeast extract, textured vegetable protein, natural flavoring, or monosodium glutamate, for example). This author questioned the possible unwitting bias in placebo material in a letter to the editor of the American Journal of Clinical Nutrition. The letter was not published and no informative reply was received. The author questioned Dr. Feldman about the contents of the placebo. He replied that he did not know the contents of the various materials used.

A 1977 study by Heywood et al.(166) which focused on neurotoxicity, came to the same conclusion as Anantharaman. Heywood et al. concluded from one study of ad libitum feeding of monosodium glutamate over a period of four days, using 20 day old mice, that, "There is indeed no evidence from any dietary study yet reported that would suggest a lack of safety of MSG as a food additive."  Details of the amounts of monosodium glutamate consumed are not given. In the discussion where it states that "...dose levels as high as 45.5 g [monosodium glutamate]/kg body weight were achieved...", we are not told if that is per day, per animal, or total. Nemeroff(126) noted that their study did not present representative histological micrographs for evaluation(152).

In a second 1979 report, Takasaki et al.(167) again reviewed a number of studies and this time reported that, among other things, "Weanling, pregnant, and lactating mice fed large amounts of MSG in the diet ... did not develop hypothalamic lesions." As evidence they cited studies by Semprini et al.(168), Huang et al.(161), Wen et al.(157), and Takasaki (162). In addition, they reported findings from their own research(167) which compared the effects of monosodium glutamate fed ad libitum to other routes of administration. In their report, they build from a discussion of findings of brain lesions to relationships of lesions to plasma glutamate levels, to relation of ad libitum dietary feeding to plasma monosodium glutamate levels, to histological effects of ad libitum feeding of monosodium glutamate, to the statement that "...plasma glutamate levels... remained much lower than those required to induce hypothalamic lesions." (Emphasis added.) It must be understood that it has never been determined that any particular level of plasma monosodium glutamate is required for the production of brain lesions.

Unfortunately, Takasaki(167) did not provide sufficient detail for one to evaluate the reports, and the reports, themselves, are lacking. Again, it will be observed that Wen(160) appears to have used the same techniques as Adamo and Ratner(131) and Oser(132) which Olney(60,133) and Burde(73) criticized in 1971.

A study by Iwata(108) failed to find behavioral abnormalities as a function of ingestion of monosodium glutamate.  Iwata did not examine the brains histologically, yet concluded that there had to be lesion damage prior to there being behavioral effects. Iwata concluded that "...dietary administration... caused no behavioral latent effect in later life." (Emphasis added.)

Prabhu et al.(169) failed to demonstrate differences in a battery of behavioral tests and drug applications. They mentioned that the results are based on surviving mice, but fail to state the mortality rate.  Lengvari(170) also reported no differences between control and experimental groups in a number of variables. One must question the meaning of their failure to find a significant difference when they report a mortality rate of 45.1% (at day 30) as opposed to a 20% mortality rate for controls.

Related, but with a slightly different focus, are a pair of studies reported by Takasaki in 1979(84) and 1980(85), in which he studied the effect on brain lesions of administering various materials simultaneously with monosodium glutamate. Takasaki reported that certain mono- and disaccharides and arginine hydrochloride, leucine and the prior injection of insulin significantly reduced the number of necrotic neurons in the arcuate nucleus of the hypothalamus. In general, the detail provided about the study is incomplete, and the procedure is difficult to follow. It is not clear whether reduction in effect of monosodium glutamate might have been due to inclusion of additional materials, thus diluting the test material. Moreover, statistics pertaining to the values for number of necrosed neurons observed appear to be based on analysis of one representative section from each animal. And values for representative brain sections appearing in Tables 1 and 2(82) have vastly different values (195 +/- 18 and 263 +/- 15) for what would appear should be the same thing. One is compelled to question the meaning of "representative" under these circumstances.

In the research report of Heywood and Worden(152) reports of lesions (or failure to find lesions) were accompanied by discussion of plasma glutamate levels and levels of glutamate found in the brain.  According to Heywood and Worden, Perez and Olney had found that "A fourfold increase in the levels of glutamate in the arcuate nucleus of the hypothalamus followed the elevation of plasma glutamate after a single subcutaneous injection of MSG. Peak plasma levels occurred after 15 min, and peak levels in the arcuate nucleus were attained after 3 hr."  Heywood and Worden(152), not Perez and Olney(63), went on to conclude that "The results indicate that plasma concentrations above a certain level were necessary to induce brain lesions." (Emphasis added.)

Today’s use of monosodium glutamate as a tool for killing brain cells

By the early 1980s, the neurotoxicity of glutamic acid in animals was generally accepted by the scientific community, and monosodium glutamate was being used as an ablative and/or provocative tool with which suspected pathophysiological abnormalities (obesity, for example) could be deliberately induced to facilitate study(123,171).

Today, researchers often use monosodium glutamate as an ablative or provocative tool(172-173).

For the truth, the whole truth, and nothing but the truth about processed (manufactured) free glutamic acid (MSG) visit us at


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Wednesday, April 20, 2011

Retinal Degeneration: Early Evidence of MSG Toxicity

Evidence of risk posed by ingestion of processed (manufactured) free glutamic acid (MSG) is undeniable.  Retinal damage induced by treatment with monosodium glutamate was demonstrated in 1957 by Lucas and Newhouse.  In 1969, Olney demonstrated that treatment with monosodium glutamate causes brain lesions in experimental animals, and that those lesions may be followed by endocrine disorders as the animals approached maturity.  During the 1970s, additional research demonstrated that hydrolyzed protein products (which contain MSG just as monosodium glutamate does) will cause brain lesions and neuroendocrine disorders; and that ingestion of monosodium glutamate by the very young will do the same.

The glutamate industry, led by Ajinomoto Co., Inc., the world’s largest producer of monosodium glutamate, responded.  Their researchers claimed to replicate the studies that demonstrated MSG-induced neurotoxicity, but did not do so.  Delay in examination of potentially damaged tissue beyond the time that damage could be observed, and delay in administering or feeding monosodium glutamate to test animals beyond the age that brain damage would most readily be inflicted, were common to these studies. Researchers also used entirely different (and inappropriate) methods of preservation and staining brain tissue in analysis of results.

As evidence of MSG-induced neurotoxicity became undeniable, the glutamate industry gave up producing its badly flawed animal studies and turned to designing, producing, and publishing human studies that seem to have been carefully designed to guarantee that no difference would be found between subjects given MSG test material and control subjects or between subjects given MSG and subjects given placebos.  It was from these studies that they would argue that ingestion of MSG poses no risk to humans.

Today, despite scientific evidence to the contrary, the people who produce and sell products that contain MSG, and their friends at the U.S. Food and Drug Administration (FDA), claim that here are a few people, but only a few people, who will suffer adverse reactions following ingestion of MSG; and that their reactions will be mild and transitory.  Similarly, industry claims that it will take a fairly substantial dose of MSG to cause an adverse reaction--a claim that cannot be substantiated because it is literally untrue.

As you read through the studies in this post and in posts that follow, please note that evidence of MSG-induced toxicity rarely comes from researchers in the United States any more.  In the United States, researchers who might criticise the safety of MSG are generally not funded, and research done independent of outside funding is generally not published.

MSG Induced Retinal Degeneration

In 1957, Lucas and Newhouse(1) first noticed that severe retinal lesions could be produced in suckling mice (and to some extent in adult mice) by a single injection of glutamate. Studies confirming their findings using neonatal rodents (2-5) and adult rabbits(6) followed shortly, with others being reported from time to time(7-11). These studies concerned themselves not only with the confirmation of monosodium glutamate induced retinal lesions, but with the formulation and testing of hypotheses to explain the phenomenon.

Between 1971 (the date of the last study referenced above) and 2002, there were studies discussing the role of glutamate in diseases of the retina, but no feeding studies.  Most, if not all of this research, was done with an eye toward developing pharmaceuticals with which to counter glutamate toxicity related to vision.  A number of these studies are cited here as examples of ongoing research(12-18).

In 2002, Ohguro et al.(19) found that rats fed 10 grams of sodium glutamate (97.5% sodium glutamate and 2.5% sodium ribonucleotide) added to a 100 gram daily diet for as little as 3 months had a significant increase in amount of glutamic acid in vitreous, had damage to the retina, and had deficits in retinal function. Ohguro et al. also documented the cumulative effect of damage caused by daily ingestion of MSG.

Subsequently, reports of toxic effects of monosodium glutamate on the retina have come from studies at the University of Pecs, Hungary, where the neuroprotective effects of PACAP in the retina have been studied(20-21).
1. Lucas DR, Newhouse JP. The toxic effect of sodium-L-glutamate on the inner layers of the retina. AMA Arch Ophthalmol. 1957;58(2):193-201.
2. Potts AM, Modrell RW,  Kingsbury C. Permanent fractionation of the electroretinogram by sodium glutamate. Am J Ophthalmol. 1960;50(Nov): 900-907.
3. Freedman JK,  Potts AM. Repression of glutaminase I in the rat retina by administration of sodium-L-glutamate. Invest Ophthalmol Vis Sci. 1962;1(Feb):118-121.
4. Freedman JK, Potts AM. Repression of glutaminase I in the rat retina by administration of sodium-L-glutamate II. Invest Ophthal Vis Sci. 1963;2(June):252-258.
5. Potts AM. Selective action of chemical agents on individual retinal layers. In: Graymore CN, ed. Biochemistry of the retina.  New York: Academic Press; 1965:155-161.
6. Hamatsu T. Experimental studies on the effect of sodium iodate and sodium L-glutamate on ERG and histological structure of retina in adult rabbits. Acta Soc Ophthalmol Jpn. 1964;68(11):1621-1636. (Abstract)
7. Hansson HA. Ultrastructure studies on long-term effects of MSG on rat retina. Virchows Arch [Zellpathol]. 1970;6(1):1-11.
8. Cohen AI. An electron microscopic study of the modification by monosodium glutamate of the retinas of normal and "rodless" mice. Am J Anat. 1967;120(2): 319-356.
9. Olney JW. Glutamate-induced retinal degeneration in neonatal mice. Electron-microscopy of the acutely evolving lesion. J Neuropathol Exp Neurol 1969;28(3):455-474. 
10. Hansson HA. Scanning electron microscopic studies on the long term effects of sodium glutamate on the rat retina. Virchows Arch ABT B (Zellpathol). 1970; 4(4): 357-367.
11. Arees E, Sandrew B, Mayer J. MSG-induced optic pathway lesions in infant mice following subcutaneous injection. Fed Proc. 1971;30(2):287Abs (Abstract # 521).
12.Casper DS, Trelstad RL, Reif-Lehrer L. Glutamate-induced cellular injury in isolated chick embryo retina: Müller cell localization of initial effects. J Comp Neurol. 1982 Jul 20;209(1):79-90.
13. Katz A, Kruger EF, Minko G, Liu CH, Rosen RB, Alfano RR. Detection of glutamate in the eye by Raman spectroscopy. J Biomed Opt. 2003 Apr;8(2):167-72.
14. Van Rijn CM, Marani E, Rietveld WJ. The neurotoxic effect of monosodium glutamate (MSG) on the retinal ganglion cells of the albino rat. Histol Histopathol. 1986 Jul;1(3):291-5.
15. Azuma N, Kawamura M, Kohsaka S. [Morphological and immunohistochemical studies on degenerative changes of the retina and the optic nerve in neonatal rats injected with monosodium-L-glutamate]. Nippon Ganka Gakkai Zasshi. 1989 Jan;93(1):72-9. [Article in Japanese]
16. Bellhorn RW, Lipman DA, Confino J, Burns MS. Effect of monosodium glutamate on retinal vessel development and permeability in rats. Invest Ophthalmol Vis Sci. 1981 Aug;21(2):237-47.

17. Fang JH, Wang XH, Xu ZR, Jiang FG. Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage. BMC Neurosci. 2010 Mar 3;11:31.
18. Varga B, Szabadfi K, Kiss P, Fabian E, Tamas A, Griecs M, Gabriel R, Reglodi D, Kemeny-Beke A, Pamer Z, Biro Z, Tosaki A, Atlasz T, Juhasz B. PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study. J Mol Neurosci. 2011 Jan;43(1):44-50. Epub 2010 Jun 22.
19. Ohguro H, Katsushima H, Maruyama I, et al. A high dietary intake of sodium glutamate as flavoring (Ajinomoto) causes gross changes in retinal morphology and function. Exp Eye Res. 2002;75(3):307-15.
20. Babai N, Atlasz T, Tamas A, et al. Search for the optimal monosodium glutamate treatment schedule to study the neuroprotective effects of PACAP in the retina. Ann N Y Acad Sci. 2006;1070(July):149-155.
21. Szabadfi K, Atlasz T, Horvath G, et al. Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment in rats. Brain Res. 2009;1259(March):107-12.