Garlic for the common cold
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine whether garlic (allium sativum) is effective for either the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.
Background
Description of the condition
The common cold is a heterogenous group of diseases caused by numerous viruses that belong to several different families (Heikkinen 2003). The viruses include picornaviruses (notably, rhinoviruses and enteroviruses), coronaviruses, adenoviruses, parainfluenza viruses, influenza viruses, metapneumoviruses and respiratory syncytial viruses (Fendrick 2003). They all cause the common symptoms of nasal stuffiness and discharge, sneezing, sore throat and cough. Other symptoms may also include hoarseness, headache, malaise and lethargy (Heikkinen 2003). The transmission of viruses occurs via contact with secretions or small‐ or large‐particle aerosols (Heikkinen 2003). On average, children have six to eight, and adults two to four colds per year (Heikkinen 2003).
The total annual economic impact of the common cold is estimated at $40 billion in the USA, including the financial impact of medical costs, days off work and the possibility of severe complications in at‐risk groups (Fendrick 2003).
Because of the many different virus types, all with varying pathogenetic mechanisms, it is understandable that an effective universal treatment for the common cold has not been developed (Heikkinen 2003). Current treatments aim to relieve the symptoms of the common cold. Antihistamines may improve a runny nose and sneezing and decongestants (norephedrine, oxymetazoline, or pseudoephedrine) provide short term (3 to 10 hours) relief of congestive symptoms (Arroll 2005). Many other treatments have an unknown effectiveness, including analgesics or anti‐inflammatory drugs, echinacea, steam inhalation, vitamin C and zinc (intranasal gel or lozenges) (Arroll 2005).
Description of the intervention
The common cold is one of the most common medical conditions treated by herbal remedies. In the USA, $5.1 billion is spent annually on herbal remedies; garlic supplements take 19.9% of this market (Barnes 2004; Ernst 2005). Garlic is commonly used to treat cardiovascular disease and cancer (AHRQ 2000). Few prevalence surveys of garlic use also report the indication it was used for (Barnes 2004; Harris 2000; MacLennan 2006), however, many manufacturers of garlic supplements claim their products boost the immune system and assist in the prevention and treatment of the common cold. Thus we can deduce that garlic supplements are commonly used by consumers for this purpose. Data from the USA confirms their popularity: in 2002, 3.76% of the population used garlic supplements (Barnes 2004). The prevalence of use of herbal medicines seems to be relatively consistent between Western countries (Harris 2000; MacLennan 2006).
Garlic (allium sativum) has been traditionally used as a medicinal plant (Rivlin 2001). Its purported range of effects include lowering of cholesterol and triglyceride levels, blood pressure‐lowering, anticoagulation, acting as an immunomodifier and an anti‐carcinogen; as well as having antimicrobial, antifungal and antiviral effects (Ankri 1999; Kyo 2001; NCCAM 2006; Ruddock 2005).
How the intervention might work
Garlic formulations include raw garlic and commercial preparations including powders, oil and aged extracts (Ruddock 2005; Staba 2001). The mechanism of action of garlic is unknown, but garlic supplements can contain allicin, ajoene and many sulphur‐containing compounds (Ankri 1999; Ruddock 2005). Allicin and ajoene have exhibited some antimicrobial activity in‐vitro (Ankri 1999; Feldberg 1988; Ruddock 2005), however the amount of these compounds present in commercial garlic preparations varies according to the process used to formulate the product (Miller 2000; Ruddock 2005; Staba 2001). These properties have led some to take an interest in the possible therapeutic benefits of garlic to treat the common cold.
Why it is important to do this review
Systematic reviews of garlic for cholesterol‐lowering and hypertension have been conducted (AHRQ 2000; Silagy 1994). However there is no systematic review of evidence for use of garlic for the common cold; this proposed Cochrane review will examine the evidence. A systematic review of the efficacy of garlic for the common cold is important in order to assist the consumer in choosing a cost‐effective treatment.
Objectives
To determine whether garlic (allium sativum) is effective for either the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.
Methods
Criteria for considering studies for this review
Types of studies
To be eligible for inclusion, studies must be randomised or quasi‐randomised trials, comparing garlic with placebo, no treatment or standard treatment. Open‐label trials will only be included if there is a blinded outcome assessment. Non‐English language trials will be included. Studies might be published or unpublished. Abstracts will not be included unless we are able to obtain further details from the investigators.
Types of participants
Trials in adults (18 years or older) and children (17 years or younger) will be included but analysed separately. Participants should have no other acute illnesses or severe chronic conditions. In treatment trials, participants should have a common cold or non‐specific viral upper respiratory tract infection. In prevention trials, 'cases' will be those who develop a common cold during the course of the study. Symptoms which should be used to identify the common cold may include coryza, sore throat, rhinitis, headache and general malaise. Studies in which the illness definition included myalgia and fever greater than 380C will be excluded, as these are common distinguishing features of influenza. Studies where participants had suspected or confirmed influenza will also be excluded.
Types of interventions
Garlic, in any medicinal formulation will be included, however only trials where garlic is the single active ingredient will be assessed. Trials where the intervention group receives other treatments in addition to garlic will be included as long as additional treatments are also given to the control group. Different garlic extracts will be included, but not trials where raw, unprocessed garlic was the intervention. Trials will not be excluded on the basis of dose, however if there are consistent discrepancies between doses used in trials, the analysis will be stratified accordingly (for example, high dose and low dose).
Types of outcome measures
For treatment trials, the primary outcome measure of interest will be the duration of symptoms of the common cold. Secondary outcomes will include severity of symptoms and functional measures such as ability to perform normal activities. Duration of illness should be measured according to the number of days or hours where symptoms are present. Symptoms should be measured objectively, according to predefined criteria (for example, rhinitis, cough, sore throat). Severity and functioning might be measured subjectively but in a format that allows comparison (for example, a Likert scale or categorical questionnaire score).
For prevention trials, the primary outcome will be the number of occurrences of the common cold. Occurrences should be measured according to an acceptable case definition of the common cold as described above. Secondary outcomes will include the duration of the common cold and the severity of symptoms as for treatment trials.
Adverse effects reported in trials will also be considered. A separate search for adverse effects will be undertaken, as clinical trial evidence may provide insufficient information.
Search methods for identification of studies
Electronic searches
The following electronic databases will be searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library latest issue) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to present); OLDMEDLINE (1950 to 1965); EMBASE (1974 to present); and AMED (1985 to present).
The following search terms will be used to search MEDLINE. These terms will be modified to search CENTRAL, EMBASE and AMED as required.
exp Garlic/ OR garlic OR exp Allium/ OR allium OR (allium sativum OR allicor OR allicin)
AND
exp Common Cold/ OR common cold$ OR (coryza OR acute nasopharyngitis) OR exp Rhinovirus/ OR rhinovirus infection$ OR exp Adenoviridae/ OR adenovirus$ OR exp Respiratory Syncytial Viruses/ OR exp Respiratory Syncytial Virus Infections/ OR (respiratory syncytial virus$ or RSV) OR exp Coronavirus OR exp Coronavirus Infections/ OR exp Respiratory Tract Infections/ OR respiratory tract infection$ OR respiratory infection$
Searching other resources
There will be no language restrictions. We will hand search the references of all identified studies. Two review authors (AB and EL) and an expert librarian will carry out the search. We will also contact the manufacturers of garlic supplements, experts in the field and the Cochrane Complementary Medicines Field.
A search for adverse effects will be undertaken separately. Acceptable study types for this search will include observational studies and case‐series. It is recognised that quantification of adverse effect rates may not be possible with this strategy. Standard reference sources will also be consulted. A search strategy to identify adverse effects might include the following MEDLINE subheadings (Higgins 2005):
/adverse effects
/poisoning
/toxicity
/chemically induced
/contraindications
/complications
Data collection and analysis
Selection of studies
Two review authors will independently review and select trials from searches, assess and rate study quality and extract relevant data. Disagreements will be resolved through discussion and consensus, or by consulting a third author. Trial authors will be contacted to request missing data or to clarify methods whenever possible.
Data extraction and management
Data will be extracted using a standardised form. The data extraction form will be revised if necessary. Information extracted will include:
age and gender of participant
number of participants
whether analysis is by intention‐to‐treat
randomisation method
method of blinding
blinding of outcome assessment
smoking or non‐smoking status
pre‐existing chronic conditions
exclusion criteria
diagnostic criteria
treatment setting
duration of treatment
outcomes
duration of illness
functioning (for example, time to return to normal activity)
severity of illness
occurrence of illness (prevention trials)
adverse effects
other medicines being used, including those with potential drug interactions.
Assessment of risk of bias in included studies
As with any systematic review, trials of poor quality may overestimate the treatment effect. The aspects of trial quality which are most important include:
Quality of randomisation
Quality of blinding (allocation concealment)
Blinding of assessment
Analysis by intention‐to‐treat
Specification of the dose, and standardisation of the garlic extract are important for generalisability, but should not affect quality.
We will assess trial quality according to the above. Any other factors that are considered to limit quality will be noted. As some studies may meet inclusion criteria but be of low quality, we will conduct a sensitivity analysis to determine the effect of poor quality trials on the effect. The sensitivity analysis will exclude trials considered poor in one or more of the aspects above. If all trials are of poor quality we will not conduct a meta‐analysis.
Unit of analysis issues
Analysis will be by intention‐to‐treat. Where results are reported using a per protocol analysis, we will use the number randomised to treatment when determining outcomes. If the trials are sufficiently similar, a meta‐analysis will be conducted. Each outcome measure will be meta‐analysed, however if there is a lack of standardisation in outcome measures, then we will use standardised mean differences to determine the overall effect size.
Analysis will be by fixed‐effect. However if there is evidence of heterogeneity, a random‐effects model will be used.
Expected sources of heterogeneity include: treatment setting, duration of treatment (for prevention trials), dose and type of extract, and variation in the outcome assessment (subjective, objective or type of questionnaire), as well as trial quality. If there is evidence of heterogeneity (according to either chi squared; P < 0.1 or I2 > 50%) and adequate data are available we will conduct subgroup analyses according to these factors.
There may be insufficient data to conduct a meta‐analysis of adverse effects and these may have been collected using different methods. We will report rates of adverse effects, and where logical, we will compare their likelihood using odds ratios.
