Monosodium glutamate avoidance for chronic asthma in adults and children
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The three objectives of this study are to
1. Identify randomised controlled trials of MSG ingestion and asthma response in adults and children (> 2 years of age) with asthma.
2. Assess the methodological quality of these trials.
3. To determine the effect of MSG ingestion on asthma.
Background
Monosodium glutamate (MSG) is the sodium salt of the non‐essential amino acid glutamic acid, and is used as a flavour enhancer. It exists both as a "free" glutamate and "bound" in protein. Glutamate is present in virtually all proteins in peptide form and is a neurotransmitter of the parasympathetic nervous system. Large amounts are synthesised and metabolised in the brain and it plays an essential role in human metabolism as it is a key component of the citric acid and other metabolic cycles (Filer 1994). It is only the "free" (L‐glutamic acid) form of glutamate which acts as a flavour enhancer (Davey 1991). The effect of L‐glutamic acid is the same regardless of whether it is from a 'natural' source or whether it has been added to the cooking or manufacturing process.
Monosodium glutamate (MSG) was first implicated in causing adverse reactions in 1968, when Dr. Kwok wrote a letter to the New England Journal of Medicine explaining how he felt after eating in a Chinese restaurant (Kwok 1968). The symptoms were burning, tightness or numbness in the upper chest, neck and face. This syndrome was named "Chinese Restaurant Syndrome". Kwok hypothesised that this syndrome could be due to MSG, sodium or some other unidentified substance.
In 1981, Allen and Baker, reported two cases of MSG‐induced asthma and proposed a possible association between asthma and MSG (Allen 1981). Over the last two decades there have been several studies looking at whether MSG ingestion can induce an asthma response, and there are several reviews on this topic (ILSI 1991; Stevenson 2000; Woods 2001) ‐ but as yet no meta‐analysis or Cochrane review has been performed to clarify the situation.
Objectives
The three objectives of this study are to
1. Identify randomised controlled trials of MSG ingestion and asthma response in adults and children (> 2 years of age) with asthma.
2. Assess the methodological quality of these trials.
3. To determine the effect of MSG ingestion on asthma.
Methods
Criteria for considering studies for this review
Types of studies
Studies have to be randomised controlled trials.
Types of participants
Only studies which focus upon asthma will be included, however the results of studies in related conditions will be considered if the results for the subjects with asthma can be identified separately. Studies in infants less than two years of age will be excluded.
Types of interventions
Any challenge of MSG to the diet and/or any manipulation of dietary intake of MSG. Only the oral route of administration will be considered (either capsule, liquid or other oral route). Double‐blind trials are preferred, but single blind and open studies will also be reviewed for possible inclusion.
Types of outcome measures
It is anticipated that not all studies will have results pertaining to all of the outcome measures listed below. However only studies which have at least one of the outcome measures will be included. Data will be analysed on an intention to treat basis wherever possible.
The outcome measures of interest are:
1. Lung function measurements such as Forced Expiratory Volume in one second (FEV1), and/or Peak Expiratory Flow (PEF) and/or Forced Vital Capacity (FVC).
2. Asthma symptom scores
3. Bronchial hyperresponsiveness (BHR)
4. Soluble inflammatory markers such as Eosinophilic Cationic Protein (ECP) and/or Tryptase
5. Asthma medication usage
6. Hospital admissions
Search methods for identification of studies
Search strategy for identification of studies
A search will be carried out of the Cochrane Airways group "Asthma and Wheez* RCT" ProCite specialised register. There will be no language restriction.
The database will use the terms:
MSG or "monosodium glutamate*" or monoglutamate or monosodiumglutamate or *sodium or sodium* or glutam* or Glutavene or L‐glutamic or L‐glu or accent or vestin or (food* and (salt* or additive* or flavour* or flavor*))
Bibliographies of existing trials will be searched and primary trial authors and MSG manufacturing companies will be approached for additional trials (both published and unpublished). An advanced search of CENTRAL, the Cochrane Controlled Trials Register will be completed using the same search strategy. A further search will be performed using Current Contents. Finally, personal contact with colleagues, collaborators and other triallists working in the field of food‐induced asthma and/or food allergy will be made to identify potentially relevant studies.
Data collection and analysis
Inclusion of studies:
From the title, abstract or descriptors, one reviewer (YZ) will review the literature searches to identify potentially relevant trials for full review. Searches of bibliographies and texts will be conducted to identify additional studies. Both reviewers will independently read the abstract and methods sections of the papers to select the trials for inclusion in this review, using specific criteria. Differences between reviewers will be measured by consensus.
Data extraction:
Data for the trials will be extracted independently by both reviewers. Principal investigators of included studies will be contacted, when required, to provide additional data or confirmation of methodological aspects of the study in order to enhance the results of this review.
Data in table or graphic form will be used if published and authors will be requested to confirm data extraction and provide clarification and additional information for the review. Studies to be included will be subjected to quality assessment by both reviewers. Trials will be combined using Review Manager 4.1.
Statistical considerations:
For continuous variables the results of individual studies will be calculated as fixed effects weighted mean difference (WMD) or standardised mean difference (SMD), with 95% Confidence Intervals (CI). For similar studies the pooled WMD or SMD and 95%CI will be calculated. Where the outcome of interest is expressed as the same scale for all included studies the WMD and 95% CI's will be calculated. Where different scales are used to measure the same outcome, the SMD and 95% CI's will be calculated. For both methods, random and fixed effect models will be compared. Where there is a significant difference in the pooled effect sizes and their 95% CI's between the random and fixed effect models, the random effect model will be used. For pooled effects a Breslow‐Day test of heterogeneity will be carried out.
For dichotomous variables, individual and pooled statistics will be calculated as odds ratios (OR) with 95% CI's.
Funnel plots will be performed to test for publication bias. If heterogeneity is found, sensitivity analyses will be performed using methodological quality as the categorising variable.
The planned analyses include:
Comparison 1: MSG administration versus placebo
Comparison 2: MSG administration versus untreated control
Comparison 3: where different doses of MSG challenge were used, dose‐response analyses will be attempted.
Comparison 4: a subgroup comparison of children versus adults will be performed, if adequate studies are found.
These comparisons will be performed separately for each outcome measure.
