Evidence of monosodium glutamate-induced adverse reactions: Double blind studies

 

As evidence of MSG-induced brain lesions and endocrine disorders was confirmed by neuroscientists, and the glutes could no longer claim that monosodium glutamate did not cause brain damage and endocrine disorders in laboratory animals, the glutes turned to production of carefully designed human studies that limited the number of adverse reaction reported, and would allow them to conclude that no relationship between MSG ingestion and adverse reactions had been found.

 

Careful review of the data presented in almost every published study will demonstrate that a number of subjects experienced adverse reactions following ingestion of monosodium glutamate test material. In every case, those data were essentially ignored in data analyses, presentation of results, and subsequent discussion.

 

 

Glutamate-Industry-Sponsored Human Studies:

Subject Selection and Methodology Favoring Production of Negative Results

(Compiled May 1, 2009)

 

 

AUTHORS

 

 

 

 

FUNDING SOURCES

 

BIAS TOWARD SELECTING SUBJECTS WHO MIGHT NOT BE SENSITIVE TO MONOSODIUM GLUTAMATE

 

BIAS TOWARD

REDUCING THE LIKELIHOOD THAT SUBJECTS WOULD REACT TO MONOSODIUM GLUTAMATE TEST MATERIAL

 

 

USE OF TOXIC OR ALLERGENIC MATERIAL IN PLACEBOS

 

 

 

USE OF TOO FEW SUBJECTS

 

FOCUS ON VARIABLES IRRELEVANT TO PRODUCTION OF ADVERSE REACTIONS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Altman DR, Fitzgerald T, Chiaramote LT. (1994)

 

Allerx

 

IGTC

 

Stipend given

 

no other information provided

 

Not all reactions were recorded

 

no other information

 

3 different doses in a liquid vehicle

 

IGTC placebos contained aspartame at the time.

 

 

 

 

 

 

 

Bazzano G, D=Elia JA, Olson RE. (1970)

 

Public Health Service

 

Adult males

 

no other information provided

 

Not all reactions were recorded

 

no other information

 

Amino acid formula with glutamate as a basic diet

 

 

 

11

 

Neurologic function; Hepatic function; Serum cholesterol; Weight.

 

Fernstrom JD, Cameron JL, Fernstrom M, McConaha C, Weltzin TE, Kaye WH. (1996)

 

IGTC

NIH

 

Well subjects

 

Informed consent

 

 

 

 

 

 

Beverage1

 

IGTC placebos contained aspartame at the time.

 

8

 

Plasma glutamate; Change in plasma glutamate; Pituitary hormone secretion.


 

 

Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, Ditto AM, Harris KE, Shaughnessy MA, Yarnold PR, Corren J, Saxon A. (2000)

 

IGTC

 

Stipend given

 

Informed consent

 

Used capsules

 

Not all reactions were recorded

 

Observation time was inadequate

 

Part 1:@Citrus-flavored beverage.@2

 

Part 2: Capsules containing sucrose

 

IGTC placebos contained aspartame at the time the study was initiated.

 

 

 

Reproducible response;3

 

Pulse; Blood pressure; Respiratory rate;

 

Relative risk

 

Germano P, Cohen SG, Hahn B, Metcalfe DD. (1991)

 

no information given

 

13 non-asthmatic and 30 asthmatic adults

 

Not all reactions were recorded

 

Used capsules

 

no information provided

 

IGTC placebos contained aspartame at the time.

 

13+30

 

1

 

 

 

Germano P, Cohen SG, Hibbard V, Metcalfe DD. (1993)

 

no information given

 

21 adults with a history of asthma

 

Not all reactions were recorded

 

Used capsules

 

no information provided

 

IGTC placebos contained aspartame at the time.

 

21

 

10

 

 

Goldschmiedt M, Redfern JS, Feldman M. (1990)

 

Ajinomoto; NIH; ILSI; VA.

 

Well subjects

 

Informed consent

 

 

 

180 mL worm beef consomme soup supplied by Ajinomoto Co., Inc. Tokyo

 

17

 

15

 

Variables were relevant to the study done, but irrelevant to adverse reactions to MSG

 

 

 Kenney RA. (1979)

 

Part 1.

 

IGTC ( with thanks to NESTEC)

 

 

Well subjects

 

Informed consent

 

Test material was given with carbohydrates

 

Not all reactions were recorded

 

Observation time was inadequate

 

Tomato juice with common salt.

 

 

 

51

 

16

 

 

 

Kenney RA. (1979)

 

Part 2.

 

IGTC

 

Informed consent

 

Observation time was inadequate

 

Sucrose; citric acid; trisodium-citrate; lemon flavor; caramel color; naringin.

 

 

57

 

16

 

 


 

 

Kenney, R.A. (1986)

 

IGTC

 

no information provided

 

Not all reactions were recorded

 

A...soft-drink solution....@

 

IGTC placebos contained aspartame at the time.

 

6

 

Objective parameters (routine chemical analyses)

 

Kerr GR, Wu-Lee M, El-Lozy M, McGandy R, Stare F.J. (1979)

 

Ajinomoto USA

 

Randomly drawn stratified random sample

 

Not all reactions were recorded

 

Observation time was inadequate

 

Questionnaire survey

 

 

 

 

 

 

Morselli P, Garattini S. (1970)

 

COFAG (IGTC Europe)

 

Well subjects

 

Test material was given with carbohydrates

 

Observation time was inadequate

 

Beef broth (ingredients not specified) followed by meat, vegetables, and fruit

 

24

 

Blood pressure; Pulse; Respiration rate

 

Prawirohardjono W, Dwiprahasto I, Astuti I, Hadiwandowo S, Kristin E, Muhammad M, Kelly MF. (2000)

 

IGTC

 

Well subjects

 

Stipend given

 

Informed consent

 

Small amounts of test material were given with carbohydrates

 

Used capsules

 

 

Lactose in gelatin capsules

 

 

 

 

52

 

Blood pressure; Pulse; Respiratory rate

 

Rosenblum L, Bradley J, Coulston F. (1971)

 

no information given

 

Males only

 

Informed consent

 

Not all reactions were recorded

 

Observation time was inadequate

 

Diluted chicken stock or diluted chicken stock with sodium (ingredients not specified)

 

95

 

 

 

Schwartzstein RM, Kelleher M, Weinberger WE, Weiss JW, Drazen JM. (1987)

 

IGTC

 

Asthmatics

 

Not all reactions were recorded

 

Used capsules

 

Medication not given for 12 hours prior to testing

 

 

 

Gelatin capsule containing sodium chloride

 

12

 

 

 

Stegink LD, Filer J, Baker GL, Bell EF. (1986)

 

IGTC

 

 

 

 

Informed consent from parent

 

no other information given

 

Test material was given with carbohydrates

 

 

 

Beef consomme supplied by Ajinomoto Co., Tokyo, Japan

 

8

 

Plasma glutamate;

Plasma aspartate

 


 

 

Stevenson DD, Simon RA, Woessner KM. (1997)

 

IGTC

 

10 alleged CRS-asthmatics and 30 alleged non-CRS asthmatics

 

Subjects eliminated

 

Not all reactions were recorded

 

 

 

no information given

 

IGTC placebos contained aspartame at the time.

 

10+30

 

 

 

 

Tanphaichitr V, Srianujata S, Pothisiri P, Sammasut R, Kulapongese S. (1983)

 

IGTC

 

Well subjects

 

Not all reactions were recorded

 

Test material was given with carbohydrates

 

Four full days= menus all different, without added monosodium glutamate: this food being able to mask the addition of monosodium glutamate

 

50

 

Plasma glutamate;

Pleasantness or unpleasantness of food

 

 

 

Tanphaichitr V, Srianujata S, Leelahabul P, Kulapongse S, Patchimasiri S, Pothisiri P. (1985)

 

IGTC

 

Well subjects

 

Not all reactions were recorded

 

Test material was given with carbohydrates

 

A full day=s menu without added monosodium glutamate

 

 

 

12

 

 

 

Tarasoff L, Kelly MF. (1993)

 

IGTC

 

Well subjects

Stipend given

 

Informed consent

 

Used capsules

 

Test material was given with carbohydrates

 

Not all reactions were recorded

 

Observation time was inadequate

 

 

Both beverage and capsules:

 

Beverage specified as containing aspartame;4 prepared from powders supplied by the IGTC

 

Placebos in gelatin capsules

 

 

 

 

 

After-taste; Intensity

 

Wilkin JK (1986)

 

VA

 

Well subjects

 

Not all reactions were recorded

 

no placebo

 

6

 

 

 

Woessner KM, Simon RA, Stevenson DD (1999)

 

IGTC;

Scripps Clinic, Green Hospital, & Research Institute

 

30 asthmatics with alleged CRS asthma and 70 without

 

Informed consent

 

Subjects eliminated

 

Not all reactions were recorded

 

Test material was given with carbohydrates

 

Continued medications

 

 

5 gelatin capsules containing sucrose

 

IGTC placebos contained aspartame at the time.

 

30+70

 

30

 

 

 


 

 

Yang WH, Drouin MA, Herbert M, Mao Y. (1997)

 

IGTC

 

Well subjects (except subjects with symptoms of CRS were accepted)

 

Stipend given

 

Informed consent

 

 

Not all reactions were recorded

 

Two or more reactions were required to be counted as a reaction

 

Observation time was inadequate

 

Strongly citrus tasting beverage containing sucrose supplied by the IGTC

 

IGTC placebos contained aspartame at the time.

 

61

 

36

 

 

 

Zanda G, Franciosi P, Tognoin G, Risso M, Standen, SM, Morselli PL, Garattini S. (1973)

 

no information given

 

Well subjects

 

Not all reactions were recorded

 

Observation time was inadequate

 

Small amounts of test material were given with carbohydrates

 

Beef bouillon (ingredients not specified)

 

 

 

72

 

Blood pressure; Pulse rate

 

 

LEGEND

 

FUNDING SOURCES:

 

COFAG: IGTC Europe

 

IGTC: International Glutamate Technical Committee (includes manufacturers and users of monosodium glutamate)

 

ILSI: International Life Sciences Institute (often under contract to the glutamate industry)

 

IMC: International Minerals and Chemical Corporation

 

NIH: National Institutes of Health

 

VA: Veterans Administration

 

BIAS IN SELECTING SUBJECTS (Not all people are sensitive to monosodium glutamate at levels ordinarily found in food.)

 

CRS: Chinese Restaurant Syndrome: a limited number of mild and transitory reactions reported in 1968 as occurring between10 minutes and 2 hours after the start of a meal and lasting less than four hours.

 

INFORMED CONSENT, while ethically appropriate, and required of all experiments using human subjects, biases these studies.

 

MALES have been reputed to be less sensitive to MSG than females

 

STIPENDS were offered to subjects who claimed to be sensitive to MSG

 

SUBJECTS were ELIMINATED prior to the study for responding to placebos that were going to be used in the study.

 

WELL SUBJECTS would be persons who had never experienced any of the reactions alleged to be attributable to use of monosodium glutamate examples of those reactions being irritable bowel, migraine headache, asthma, skin rash, heart irregularities, mood swings, and depression.

 

BIAS TOWARD REDUCING THE LIKELIHOOD THAT SUBJECTS WOULD REACT TO MONOSODIUM GLUTAMATE TEST MATERIAL

 

CAPSULES guarantee slow release and, therefore, less effect from the material they contain

 

TEST MATERIAL GIVEN WITH CARBOHYDRATES interferes with the uptake of the test material

 

PLACEBOS

 

It would appear that in most, if not all, glutamate-industry-sponsored studies, both test and placebo material were supplied by the IGTC. According to a 1991 letter from IGTC chairman Andrew G. Ebert to LSRO-FASEB and the FDA, a Abeverage mix designed to mask the taste of [monosodium glutamate]@, was modified in 1978 to replace the [former use of] surcose with the low calorie sweetener Aspartame. Prior to the time that Northwestern University was alerted by the Truth in Labeling Campaign to the fact that aspartame was being used in placebo material being used in an IGTC-sponsored study being carried out by Geha et al. at Northwestern, Harvard, and UCLA, the use of aspartame in placebos was not acknowledged in research reports.

BEVERAGE(1): Citric acid, trisodium citrate, lemon flavoring, caramel coloring, naringenin-7-rhamnosidio-glycoside (grapefruit bitter principle), sodium saccharin; prepared by Ajinomoto


 

CITRUS-FLAVORED BEVERAGE(2): Sodium citrate, citric acid, saccharin, citrus flavor, and naringin were cited as ingredients. Aspartame was used (but not named) with the other ingredients prior to objections filed with Northwestern University by the Truth in Labeling Campaign.

 

BEVERAGE(4): Sodium citrate dihydrate, citric acid monohydrate, potassium chloride, naringin, grapefruit flavor, caramel, and aspartame.

 

IRRELEVANT VARIABLES

 

REPRODUCIBLE RESPONSE: (3) Repetition of the same two or more responses to monosodium glutamate on two occasions, and no response to the Aplacebo@ (which contained aspartame).

 

 

REFERENCES

 

Altman DR, Fitzgerald T, Chiaramonte LT. Double‑blind placebo‑controlled challenge (DBPCC) of persons

reporting adverse reactions to monosodium glutamate (MSG). J Allergy Clin Immunol. 1994;93:303 (Abstract 844).

 

Bazzano G, D=Elia JA, Olson RE. Monosodium glutamate: feeding of large amounts in man and gerbils. Science. 1970;169:1208‑1209.

 

Fernstrom JD, Cameron JL, Fernstrom MH, McConaha C, Weltzin TE, Kaye WH. Short‑term neuroendocrine

effects of a large, oral dose of monosodium glutamate in fasting male subjects. J Clin Endocrinol Metab. 1996;81:184‑191.

 

Geha R, Beiser A, Ren C, et al. Multicenter multiphase double blind placebo controlled study to evaluate alleged reactions to monosodium glutamate (MSG). J Allergy Clin Immunol. 2000;106:973-980.

 

Germano P, Cohen SG, Hahn B, Metcalfe DD. An evaluation of clinical reactions to monosodium glutamate (MSG) in asthmatics using a blinded, placebo‑controlled challenge. J Allergy Clin Immunol. 1991;87: 177 (Abstract 155).

 

Germano P, Cohen SG, Hibbard V, Metcalfe DD. Assessment of bronchial hyperactivity by methacholine challenge (MTC) in asthmatics before and after monosodium glutamate (MSG) administration. J Allergy Clin Immunol. 1993;91:340 (Abstract 798).

 

Goldschmiedt M, Redfern JS, Feldman M. Food coloring and monosodium glutamate: effects on the cephalic phase of gastric acid secretion and gastrin release in humans. Am J Clin Nutr. 1990;51:794‑797.

 

Kenney RA. Placebo‑controlled studies of human reaction to oral monosodium L‑glutamate. In Filer LJ Jr, Garattini S. Kare MR, Reynolds WA, Wurtman RJ, eds. Glutamic acid: advances in biochemistry and physiology. New York: Raven; 1979:363-373.

Kenney RA. The Chinese restaurant syndrome: an anecdote revisited. Food Chem Toxicol. 1986;24:351-354.

 

Kerr GR, Wu‑Lee M, El‑Lozy M, McGandy R, Stare FJ. Prevalence of the "Chinese restaurant syndrome." J Am Diet Assoc. 1979; 75:29‑33.

 

Morselli P, Garattini S. Monosodium‑glutamate and the Chinese restaurant syndrome. Nature. 1970;227:611‑612.

 

Prawirohardjono W, Dwiprahasto I, Astuti I, et al. The administration to Indonesians of monosodium L-glutamate in Indonesian foods; an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study. Nutr 2000; 130: 1074S-1076S.

 

Rosenblum L, Bradley J, Coulston F. Single and double blind studies with oral monosodium glutamate in man. Toxicol Appl Pharmacol 1971; 18:367-373.

 

Schwartzstein RM, Kelleher M, Weinberger WE, Weiss JW, Drazen JM. Airway effect of monosodium glutamate in subjects with chronic stable asthma. J Asthma. 1987;24:167-172

 

Stegink LD, Filer J, Baker GL, Bell EF. Plasma glutamate concentrations in 1-year-old infants and adults ingesting monosodium L-glutamate in consomme. Pediatr Res. 1986;20:53-58.

 

Stevenson DD, Simon RA, Woessner KM. The role of monosodium L‑glutamate (MSG) in asthma: does it exist? J Allergy Clin Immunol. 1997;99:S411 (Abstract 1670).

 

Tanphaichitr V, Srianujata S, Pothisiri P, Sammasut R, Kulapongese S. Postprandial responses to Thai foods with and without added monosodium L-glutamate. Nutr Rep Int. 1983;28:783-792.

 


Tanphaichitr V, Srianujata S, Leelahabul P, Kulapongse S, Patchimasiri S, Pothisiri P. Effect of monosodium L-glutamate in take on protein-calorie status in healthy Thai adults. Nutr Rep Int. 1985;32:1073-1080.

 

Tarasoff L, Kelly MF. Monosodium L‑glutamate: a double‑blind study and review. Food Chem Toxic. 1993;31:1019‑1035.

 

Wilkin JK. Does monosodium glutamate cause flushing (or merely Aglutamania@)? J Am Acad Dermatol. 1986;15:225-230.

 

Woessner KM, Simon RA, Stevenson DD. Monosodium glutamate sensitivity in asthma. J Allergy Clin Immunol. 1999; 104: 305-310.

 

Yang WH, Drouin MA, Herbert M, Mao Y. The monosodium glutamate symptom complex: assessment in a double‑blind, placebo‑controlled, randomized study. J Allergy Clin Immunol. 1997; 99:757‑762.

 

Zanda G, Franciosi P, Tognoin G, et al. A double blind study on the effects of monosodium glutamate in man. Biomedicine. 1973;19:202-204.