UM: Monosodium Glutamate (MSG) and Adverse Effects (2013)
To determine whether monosodium glutamate (MSG) ingestion induces asthma attacks in asthmatic subjects.
- History of asthma
- History of asthma attacks in Oriental restaurants, believed that MSG induced asthma attacks and were attempting to avoid MSG or had suspected aspirin sensitive asthma, were referred to Scripps Clinic for aspirin desensitization and did not have a perceived sensitivity to MSG
- Signed written consent.
- No history of asthma
- Unstable asthma during placebo challenge
- Daily dependence on salmeterol to maintain airway stability.
Recruitment
Recruited from practices, referring physicians and newspaper advertisements.
Design
- Subjects were admitted to the GCRC and a single-blind placebo challenge was performed on day two of the study for subjects whose forced expiratory volume (FEV1) baseline values were 70% or greater of their predicted value. Five placebo capsules containing 500mg sucrose each were ingested by the patient between 7:00 and 8:00 a.m. and again between 1:00 and 2:00 p.m. and FEV1 values were measured every hour and at onset of symptoms for 12 hours.
- Single-blind challenges with MSG were given on day three with 2.5g (five capsules) of MSG given between 7:00 and 8:00 a.m. with five placebo capsules given between 1:00 and 2:00 p.m. to mimic the placebo trial if during the baseline placebo challenge FEV1 values varied by less than 10% during the 12 hours of challenges and baseline FEV1 values on both days were required to be within 5% of each other. If criteria was not met, the subject was classified as having unstable airways and did not undergo MSG challenge. Hourly FEV1 measurements and recording of all signs and symptoms were performed for a total of 12 hours.
- If there were no significant changes in FEV1 values during the single-blind screening challenges, the patient was either discharged from the GCRC or proceeded to additional oral challenge studies on subsequent days
- If there was a 20% drop in FEV1 value, serum tryptase levels were determined and the patient underwent two double-blind placebo controlled MSG challenges on days four and five (two placebo and one MSG challenge were conducted for each of the two double-blind challenges).
Blinding Used
Blinding of subjects regarding placebo and MSG capsule administration for initial challenge, double-blinding used for additional challenges.
Intervention
- Placebo: 500mg sucrose
- MSG: 2.5g per day via five capsules.
Statistical Analysis
Means, SEMs, one-sided confidence intervals (CI) and paired Student T-test results compared the lowest declines in FEV1 values during the 12-hour challenges for placebo and MSG challenge days.
Timing of Measurements
- Initial telephone screening interview by the nurse coordinator or study physician to confirm history of asthma and attacks of asthma associated with ingestion of food and drink in Oriental restaurants and aspirin or other NSAIDS
- If history was suggestive, patients were scheduled for an initial visit where the diagnosis of asthma was established by either a 20% improvement in FEV1 values after agonist inhalation or positive methacholine inhalation challenge
- Complete history and physical examination as well as medication verification conducted on day one of study
- FEV1 levels measured at baseline as well as hourly and at onset of symptoms for 12 hours during placebo and MSG challenges using a wedge spirometer with integrated flow output
- Serum tryptase level measured if subject experienced a drop of more than 20% FEV1 value during MSG challenge and collected at baseline, time of reaction and one, two and three hours after drop in FEV1.
Dependent Variables
- Change in FEV1 values: 20% decline in FEV1 values from baseline with or without accompanying symptoms for necessary criteria for presumed MSG-induced asthma attack
- Serum tryptase levels.
Independent Variables
- Placebo
- MSG 2.5g.
Control Variables
- Physical reaction symptoms
- Age
- Gender
- Medications
- Medical history.
- Initial N: 142 asthmatic subjects were screened, 121 subjects were entered into the study
- Attrition (final N): 100 subjects underwent challenge with MSG; 21 patients not eligible for MSG challenge due to unstable asthma during placebo challenge
- Other relevant demographics: 30 subjects reported sensitivity to MSG and were actively avoiding MSG (group A) and 70 subjects reported no history of MSG sensitivity (group B)
- Location: California, United States.
Key Findings
- Group A (MSG history positive):
- No significant differences between percent changes in lowest recorded FEV1 values after placebo challenge compared with percent changes in lowest recorded FEV1 values after MSG oral challenge of 2.5g in this patient population (P=0.28, paired student T-test)
- Only one of 30 patients experienced 20% decline in FEV1 values during the single-blind screening challenge with MSG:
- Subject was without asthma symptoms throughout MSG challenge and serum tryptase levels were normal
- Subsequent double-blind placebo controlled MSG challenges in replicate were negative with post MSG changes in FEV1 values of less than 1%
- Exact one-sided 95% CI for probability of MSG sensitivity in subjects with perceived MSG sensitivity was 0% to 0.07%
- Group B (no history of MSG sensitivity)
- 80% of challenged subjects had documented aspirin or NSAID sensitivity (56 subjects)
- Percent predicted FEV1 mean value for entire group was 87.9% (SEM, 1.77%)
- Percent change to lowest recorded FEV1 values ranged from 0% to 10% during placebo challenge (mean 3.13%; SEM 0.66%)
- Percentage change to lowest recorded FEV1 values ranged from 0% to 13% (mean 3.67%; SEM 0.74%)
- No statistical difference in the change of lowest FEV1 values between placebo and MSG challenges in this group (P=0.44, student paired T-test)
- Exact one-sided 95% CI for probability of MSG sensitivity to subjects with aspirin sensitive asthma without a history of asthma in Oriental restaurants is 0% to 0.04%
- For both groups, seemingly random symptoms occurred on both placebo and MSG challenge days.
Other Findings
- For the 30 subjects with history of MSG sensitivity, logical reasons for their Oriental restaurant associated asthma attacks could be reasonably reconstructed for most subjects. Possible reasons included:
- Gastroesophageal reflux
- Food allergies and anxiety
- Depression
- Fear of MSG asthma attacks.
The study failed to demonstrate a relationship between ingestion of MSG and its provocation of asthma.
Industry: |
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University/Hospital: | Scripps Hospital, Green Hospital and Scripps Research Institute |
No limitations noted.
Quality Criteria Checklist: Primary Research - Non human subjects
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Relevance Questions | |||
1. | Would implementing the studied intervention, procedure, or product (if found successful) result in improved outcomes for the patients/clients/target population group? | Yes | |
2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/target population group would care about? | Yes | |
3. | Is the focus of the intervention, procedure or product (independent variable) or topic of study a common issue of concern to dietetics practice? | Yes | |
4. | Is the intervention, procedure or product feasible for application in dietetic practice? | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1.1. | Was the specific intervention(s) or procedure (independent variable(s)) or exposure factor, process or product of interest identified? | Yes | |
1.2. | Was the outcome(s) (dependent variable(s)) or status or condition of interest clearly indicated? | Yes | |
1.3. | Were the study context and setting specified? | Yes | |
2. | Was the selection of study subjects/units to be observed free from bias? | Yes | |
2.1. | Were eligibility criteria (inclusion/exclusion) specified with sufficient detail and without omitting criteria critical to the study? | Yes | |
2.2. | Were criteria applied equally to all units of observation and all study groups? | Yes | |
2.3. | Was the source and other relevant characteristics of units of observation described? | Yes | |
2.4. | Were the selected units a representative sample of the context and setting for application of study findings? | Yes | |
3. | Were study groups comparable or was an appropriate reference standard used? | Yes | |
3.1. | Was the method of assigning subjects/units of observation to groups or assigning treatment to units of observation described and unbiased? (Method of randomiztion identified if (RCT)) | Yes | |
3.2. | Was the distribution of relevant characteristics similar across subjects/units of observation and study groups at baseline? | Yes | |
3.3. | Were concurrent controls used? (Concurrent comparison data preferred over historical data.) | Yes | |
3.4. | If a cross-sectional study, were groups comparable on important confounding factors and/or were pre-existing differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
3.5. | If a diagnostic, validity or reliability study, was there a comparison with an appropriate reference standard? | N/A | |
3.5. | If a diagnostic, validity or reliability study, was there a comparison with an appropriate referene method? | N/A | |
4. | Were methods of handling losses from the original sample (withdrawals) described? | Yes | |
4.1. | Were follow-up methods described and the same for all subjects/units of observation and all groups? | Yes | |
4.2. | Were the number, characteristics of withdrawn units (i.e., damaged specimen, dropouts, lost to follow up, attrition rate), and/or response rate (cross-sectional studies) described for the sample and each group? | Yes | |
4.3. | Were all enrolled subjects/units (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawal or loss similar across groups? | No | |
4.5. | If diagnostic test, was decision to perform reference test not dependent on results of the diagnostic method under study? | N/A | |
5. | Was blinding used to prevent introduction of bias? | Yes | |
5.1. | Were field and research staff and investigators blinded to treatment group, as appropriate? | Yes | |
5.2. | Were data collectors blinded for outcomes assessment? (If the outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
5.3. | In a cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
5.5. | In diagnostic, reliability or validity study, were test results blinded to unit of observation history and other test results? | N/A | |
6. | Was the intervention/treatment regimen/exposure factor, procedure, process or product of interest and any comparison(s) described in detail? Were intervening factors described? | Yes | |
6.1. | Were protocols described for all alternatives studied? | Yes | |
6.2. | Was the context (study setting, intervention or exposure details or process, involved personnel, etc) described? | Yes | |
6.3. | Was the intensity and duration of the treatment or exposure factor sufficient to produce a meaningful effect? | Yes | |
6.4. | Was fidelity to the research plan documented and the actual amount of exposure, if relevant, measured, and are data free from bias? | Yes | |
6.5. | Were co-interventions (e.g., concurrent ancillary treatments or procedures, other therapies) described? | Yes | |
6.6. | Were extra or unplanned interventions or environmental influences during the study period described? | Yes | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all units of observation and all groups? | Yes | |
6.8. | In a diagnostic, validity or reliability study, were details of test administration and replication sufficiently described? | N/A | |
7. | Were outcomes or condition or status of interest clearly defined and the measurements valid and reliable? | Yes | |
7.1. | Were key outcomes (including primary and secondary endpoints, if applicable) described and relevant to the question? | Yes | |
7.2. | Were nutrition-related outcomes measures, if included, appropriate to the study question and outcomes of concern? | Yes | |
7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
7.5. | Was the measurement of outcome or effect at an appropriate level of precision? | Yes | |
7.6. | Were other factors that could affect outcomes (e.g., confounders) measured or accounted for? | Yes | |
7.7. | Were the measurements conducted consistently across units of observation, groups and time periods? | Yes | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
8.4. | Was there a clear description of subjects/units observed included in each analysis? If appropriate, was there a dose-response analysis? | Yes | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | No | |
8.6. | Was clinical or pragmatic significance as well as statistical significance reported? | Yes | |
8.7. | Was a power calculation reported to address adequate sample size to measure effect and avoid type 2 error? (This is especially important if findings are negative.) | No | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there an adequate discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | Yes | |
10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was there no apparent conflict of interest? | Yes | |