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Glutamate industry research on the safety of monosodium glutamate

(Compiled by Adrienne Samuels, Ph.D., September, 2010)

Studies of the safety of monosodium glutamate are just that: studies of the safety of monosodium glutamate.  All are designed, and implemented by the International Glutamate Technical Committee (IGTC) or are funded by others in the glutamate industry. The possibility of toxicity/danger is never considered. 

There were animal studies done in the 1970s by independent scientists that demonstrated, without question, that monosodium glutamate is neurotoxic (kills brain cells) and is an endocrine disruptor. (See Evidence of MSG-induced brain damage and endocrine disorders: The animal studies.)  Today, those studies are simply ignored by the glutamate industry; and the glutamate industry is so very powerful that they have been able to convince others to ignore those studies, too.

To go beyond ignoring the animal data, and move to producing human studies that industry could use to convince people that monosodium glutamate is safe for human consumption, glutamate industry researchers designed and implemented studies wherein they:

1) Selected subjects who might not be sensitive to monosodium glutamate while claiming that they were sensitive to monosodium glutamate;

2) Reduced the likelihood that subjects would react to monosodium glutamate test material;

3) Used toxic or allergenic material in placebos, so some people would likely react to placebos;

4) Used too few subjects, so there would be inadequate statistical power to produce a significant difference between adverse reactions of test subjects and placebo subjects, or inadequate statistical power to find a significant relationship between the experimental variable and the measured outcome;

5) Applied statistical tests to research designs that did not meet the tests’ underlying assumptions;

6) Focused on non-relevant variables;

7) Ignored relevant data;

8) Concluded that they found no difference between the number of adverse reactions of people who were fed monosodium glutamate and the number of adverse reactions of people who were given placebos, or concluded that subjects who were fed monosodium glutamate did not differ in some way (with higher or lower blood pressure or heart rate, for example) from people who were not fed monosodium glutamate;

and claimed that the results of those studies provided evidence that monosodium glutamate was safe.

Reviewed individually, inappropriate handling of subjects, methodology, and/or statistical analysis in any one study might be attributed to shoddy science or sloppy scholarship.  However there is sameness in these studies which lies in the fact that methodology virtually guarantees that no statistically significant difference between subjects treated with monosodium glutamate and subjects treated another way will be found; and/or no significant relationship will be found between two or more variables being investigated.  Researchers, then, can legitimately conclude that subjects who were given monosodium glutamate did not have more reactions than subjects given a placebo; or subjects consuming greater quantities of monosodium glutamate did not become taller, shorter, fatter, or thinner, and did not have more adverse reactions or higher blood pressure than others.

It is these studies that industry points to when claiming that monosodium glutamate is safe, or when claiming that the safety (never toxicity) of monosodium glutamate is controversial.  We submit, however, that since industry bases its claim for the safety of monosodium glutamate on these badly flawed studies, industry itself has demonstrated that ingestion of monosodium glutamate places consumers at risk.  There really is no controversy.

Following are details of methodology used by industry.  Not every method is used in every study.  A sample of studies in which these methods have been used will be found at Glutamate-Industry-Sponsored Human Studies.

Method 1: Not all people experience adverse reactions to MSG.  If you use people in your study who do not experience adverse reactions to MSG, you will find that none of the people you test will have adverse reactions to MSG.  So if you don’t want people reacting to the MSG you give them, use people who do not react adversely to MSG.

Thus, select subjects who claim to be sensitive to monosodium glutamate but might not be sensitive, and might not react to monosodium glutamate when ingested.  The claim of investigators will be that subjects are people who claim to be sensitive to monosodium glutamate, and the conclusion will be that people who claim to be sensitive are not really sensitive to the product.  Keys to use of this method lie with enticing subjects who are not sensitive to say that they are sensitive, while disqualifying potential subjects who might be sensitive to the product, and frightening subjects who might qualify, but fear that they might suffer adverse reactions if they participated.

a) Offer several hundred dollars to students or others who agree to participate in a study – but only if they claim to be sensitive to MSG.  It is conceivable that some people might lie about being sensitive to MSG for a prize of several hundred dollars.

b) Require that all of your subject be "well" people, i.e., people who have never had any of the reactions that can be caused by MSG;

 

c) Require that people who would participate in a study first demonstrate that they will not react to "screening placebos” that will contain toxic or allergenic material similar to the test material.  Only people who were not sensitive to the test material in the “screening placebos” would then be serving as subjects in these studies;

 

d) Require that subjects offering to participate in the study give informed consent as part of the subject screening process. Describe the study as including "treatments that might contain flavor enhancers."  It is extremely unlikely that a person who knew he was sensitive to MSG would volunteer to participate in a study where he might be asked to ingest a flavor enhancer.  MSG is advertised as a flavor enhancer. Requiring informed consent biases these studies(2,3).

 

Method 2: Minimize the likelihood that a subject will react to the test material.

 

a) Use very little monosodium glutamate in the test material;

b) Use monosodium glutamate encased in capsules. One gram monosodium glutamate encased in capsules, and therefore guaranteeing slow release, will cause less effect than 1gram monosodium glutamate sprinkled on food;

c) It has been reported that reactions to monosodium glutamate are greater on an empty stomach.  Therefore, treat all subject to a breakfast or lunch prior to starting the experiment;

d) If subjects are on medications that might block the effects of monosodium glutamate, medications for asthma or migraine headache for example, be sure that those subjects continue to take their medications while participating in the experiment;

e) Reactions to monosodium glutamate may occur immediately following ingestion of monosodium glutamate or they may occur as late as 24 or even 48 hours after ingestion of monosodium glutamate.  By recording reactions as reactions to monosodium glutamate only if they occur 2 hours or less following ingestion of test material, reactions that occur later won't be recorded as reactions to  monosodium glutamate;

f) Space MSG and control sessions so the reactions might overlap.  This will virtually guarantee that some reactions to MSG will occur during the period following administration of the placebo and be counted as reactions to the placebo.

g) Reactions to MSG are many and varied.  Limit the adverse effects to be accepted as adverse reactions to a few generally mild and transitory reactions occurring simultaneously, such as those first reported in 1968 by Kwok and dubbed "Chinese- restaurant syndrome" (CRS): "...numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitation."  By limiting the types of reaction that will be accepted as adverse reaction to monosodium glutamate, some subjects will be reacting with reactions that won't be counted as reactions to monosodium glutamate.  (Maybe that's why the glutes refer to monosodium glutamate reactions as "Chinese Restaurant Syndrome".)  If the only reactions counted as adverse reactions are limited to those of "Chinese Restaurant Syndrome," subjects who get migraine headache, skin rash, or tachycardia, for example, will not be counted as having had reactions to the monosodium glutamate test material.

Method 3: Maximize the probability the subjects will react to the placebo.

a) Use something in placebo material that will cause adverse reactions in MSG-sensitive people, i.e., use placebos virtually guaranteed to produce as many reactions as might be produced following ingestion of the monosodium glutamate test material.  Using toxic material in both test material and placebo, researchers will argue that the reactions to monosodium glutamate-containing test material are not reactions to monosodium glutamate because subjects also react to placebos. The use of toxic material in placebos, particularly when it is identical or similar to the monosodium glutamate in the monosodium glutamate test material, will make it virtually inevitable that there will be approximately as many reactions to placebos as there are reactions to monosodium glutamate test material.  In short, lace the material called “placebo” with material that will cause reactions similar to, or identical to, the adverse reactions allegedly caused by monosodium glutamate.

 

The Glutes have used both neurotoxic aspartic acid and neurotoxic glutamic acid as materials in their placebos.  Glutamic acid will be found in MSG-containing ingredients such as autolyzed yeast, citric acid, and gelatin.  Gelatin capsules are often used in these industry-sponsored studies.

Those who manufacture, sell, and promote the use of monosodium glutamate routinely restrict their use of the acronym “MSG” to refer to monosodium glutamate; and “MSG” is often used as shorthand for monosodium glutamate in the scientific literature.  When glutamate-industry researchers report that no subject has been given access to MSG during their study, it does not preclude the possibility that they may have been given processed free glutamic acid (MSG) delivered in an ingredient other than monosodium glutamate.

b) Feed all subjects breakfast, snacks, and/or lunch that contain ingredients that contain MSG; and do that 2 hours or less before the placebo trial is given.  The MSG or other neurotoxic material in this food will be added to any MSG or other neurotoxic material in the placebo, and will increase the chances that a subject might react adversely to the placebo.

c) Make no attempt during the course of the study to prevent subjects from ingesting food, drink, or dietary supplements, or chewing gum, to which they might be allergic or sensitive;

d) Schedule test and placebo treatments so a reaction to test material might occur after the placebo is given and be counted as an adverse reaction to the placebo.

Method 4: Focus on non-relevant measures.

 

a) Focus on an adverse reaction, change in blood pressure for example, that will not change, or will change only marginally when a subject ingests the test material. Use those data as basis for the claim that the test material does not cause adverse reactions;

b) Exclude some of the known relevant effects or adverse reactions from consideration.

Method 5: Subject data to sophisticated sounding inappropriate statistical analyses.

 

a) Use inferential statistics on data collected from volunteer subjects not randomly drawn from any population, thereby violating one of the tests’ underlying assumptions;

 

b) Apply statistical tests to data from research designs that fail to meet one or more of the tests’ underlying assumptions.

 

Method 6: Without considering whether or not proposed statistical tests are appropriate, minimize the probability that statistically significant relationships and/or statistically significant differences between groups being compared will be found.

a) Use such small numbers of subjects that no matter what the data show, it will be virtually impossible to get a statistically significant difference between test and placebo groups. To accomplish this, one can start with a limited number of subjects, and/or design a two-phase study wherein a number of subjects are eliminated following Phase One; 

b) Where analyses of raw data do not produce the desired results, create ratios, relative frequencies, or other indices that will reduce differences in response rate between subjects responding to test material and subjects responding to placebos.

Method 7: Draw unjustified conclusions from inappropriately interpreted statistical analyses.

Draw conclusions that do not follow from the results of the study. IGTC researchers have concluded, for example, that because approximately one third of their subjects reacted adversely to placebos containing MSG and/or aspartame, they have "proved" that reactions to MSG-containing test material are not reactions to MSG.  (In truth, all that they have demonstrated is that their placebo consuming subjects are sensitive to aspartame and/or MSG.)

The statistical models on which the inferential statistics used by the glutes are based, allow the investigators to conclude that it is highly likely (95 or 99 percent probability) that differences found were not due to chance.  The statistical models do not, however, allow investigators to conclude that there is no difference between the two groups when a statistically significant difference is not found;

Drawing conclusions based on failure to find a difference (i.e., on failure to reject the null hypothesis) is grossly inappropriate(4-6). Failure to find a statistically significant difference between groups may provide useful information for planning one's next experiment, but it proves nothing.

Method 8: Ignore relevant data; transform relevant data so that its value declines, and/or be selective about which data will be reported.

Beyond design: In addition to issues of research design and methodology, investigators have been known to:

a) Draw conclusions that do not follow from the results of their studies;

b) Minimize discussion of embarrassing data;

c) Direct readers' attention to things deemed to be of value to industry; not necessarily reporting all data or results of statistical tests;

d) Include discussion of ideas that have little or nothing to do with the results of the study;

e) In discussion, include material that industry wants presented to the public, whether or not it is relevant to the stated intent of the research;

f) Fail to publish, or even talk about, the results of studies that don't come out as planned.

 

REFERENCES

1. Samuels A. The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Account Res. 1999;6:259-310.

2. Mitchell AM, Kline JA. Systematic bias introduced by the informed consent process in a diagnostic research study.  Acad Emerg. Med 2008;15:225-30.

3. Bjarnason NH, Kampmann JP. Selection bias introduced by the informed consent process.  Lancet. 2003;361:1990.

4. Ferguson GA. Statistical Analysis in Psychology and Education. New York: McGraw-Hill; 1959.

5. Weinberg GH, Schumaker JA. Statistics: An Intuitive Approach. Belmont: Wadsworth; 1962.

6. McNemar Q. Psychological Statistics. New York: Wiley; 1949.

7. Olney JW, Ho O. Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature. 1970;227:609-10.

8. FDA Technical Information Specialist (HFS-728). Memorandum to Health Hazard Evaluation Board. Re: Summary of Adverse Reactions Attributed to MSG. June 26, 1997.

9. Federation of American Societies for Experimental Biology (FASEB). Analysis of adverse reactions to monosodium glutamate (MSG). Raiten DJ, Talbot, JM, Fisher, KD, eds. Bethesda, MD: Life Sciences Research Office, FASEB; 1995:77-79.

10. Olney JW, Ho OL, Rhee V. Brain-damaging potential of protein hydrolysates. N Engl J Med. 1973; 289:391-93.

11. FDA Bureau of Foods. Letter to a consumer from S.I. Delgado. March 3, 1981.
“...if you wish to avoid the so-called 'Chinese restaurant syndrome,' you should also avoid foods which contain hydrolized vegetable protein.”

12. Price MT, Olney JW, Lowry OH, Buchsbaum S. Uptake of exogenous glutamate and aspartate by circumventricular organs but not other regions of brain. Neurochem. 1981;36:1774-80.

13. FDA Technical Information Specialist (HFS-728). Memorandum to Health Hazard Evaluation Board. Re: Summary of Adverse Reactions Attributed to Aspartame. June 26, 1997.

14. Ebert AG. Letter to Sue Ann Anderson, R.D., Ph.D., Senior Staff Scientist, FASEB. March 22, 1991.