Peripheral arterial occlusive disease primarily affects the major arteries of the lower limb. The most common symptom in early occlusive disease is intermittent claudication - discomfort in the legs induced by exercise and relieved by rest. Numerous risk factors have been associated with the development of peripheral arterial disease, including cigarette smoking, raised blood lipids, hypertension and diabetes.
The medicinal use of garlic can be traced back to Egyptian times. The primary active component of garlic is an unstable odorous sulphurous compound called allicin. Meta-analysis of commercially available preparations of garlic have been reported to have beneficial effects on some of the risk factors associated with atherosclerosis such as serum cholesterol (Silagy 1994; Warshafsky 1993). With fresh garlic, the dosages needed to inhibit platelet aggregation or lower cholesterol levels are unacceptably high; at least seven cloves of garlic per day (Kleijnen 1989).
Garlic is an acceptable therapy to the general population and, apart from the odour, has only minor gastrointestinal side effects. Trials with endpoints more meaningful and relevant than laboratory endpoints, however, are necessary before claiming that garlic improves health. Many trials have been carried out to assess its efficacy in the treatment and risk reduction of coronary atherosclerosis, but few trials have been carried out in people with peripheral vascular disease.
The purpose of this review is to assess the efficacy of garlic therapy in improving the morbidity associated with peripheral arterial occlusive disease. The relevant trials of garlic have been considered. As one of the difficulties in showing the effectiveness of garlic is that active ingredients may be lost in processing, the type of preparation (i.e. fresh, powdered or non-powdered) has been taken into consideration.
To establish the effectiveness of garlic in the treatment of peripheral arterial occlusive diseases.
We wished to test the following hypotheses:
a) That commercially prepared garlic preparations have a beneficial effect on the morbidity associated with peripheral arterial occlusive disease;
b) That the magnitude of the effects observed with dried garlic is greater than with non-powder preparations in the treatment of peripheral arterial occlusive disease.
Criteria for considering studies for this review
Types of studies
We assessed randomised controlled trials of garlic versus placebo for the treatment of peripheral arterial occlusive disease. As there are currently only a few trials in this area, any trials identified in future that either use alternation (e.g. allocation by date of birth or days of the week) or that have not been analysed on an intention-to-treat basis (as long as all randomised patients were accounted for) will be included. Blinding of participants is a particular problem in garlic trials because of its characteristic smell.
Types of participants
People with peripheral arterial occlusive disease were included. Most participants had intermittent claudication (diagnosed either by questionnaire or clinically), but those with critical limb ischaemia and asymptomatic disease identified by testing (angiography, ankle pressures, etc.) were also eligible.
People with aortic disease and no peripheral arterial disease were excluded.
Types of interventions
Any trial of garlic therapy for the treatment of peripheral arterial occlusive disease was considered. Since one of the difficulties in showing the effectiveness of garlic is that active ingredients may be lost in processing, the type of preparation (i.e. fresh, powdered or non-powdered) was taken into consideration.
Types of outcome measures
Two main outcome measures were considered: objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing, angiography); and subjective measures (e.g. symptom progression).
Search methods for identification of studies
For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 12, part of The Cochrane Library (www.thecochranelibrary.com). See Appendix 1 for details of the search strategy used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, AMED, and through handsearching relevant journals. The full list of the databases, journals and conference proceedings which have been searched, as well as the search strategies used are described in the (Specialised Register) section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com).
Searching other resources
The reference lists of relevant studies were screened for additional studies and citation tracking of any relevant trials was carried out.
Data collection and analysis
Selection of trials
Ruth Jepson selected trials for possible inclusion in the review and sought additional information from the principal investigators of all trials.
Assessment of methodological quality
Ruth Jepson and Jos Kleijnen independently assessed the methodological quality of trials using a standard scoring sheet developed by the Cochrane PVD Review Group. Any discrepancies were considered by Gill Leng until a consensus decision could be made.
For the one included trial, information was collected about the method of randomisation, blinding and whether an intention-to-treat analysis could possibly be done. Ruth Jepson and Jos Kleijnen extracted data independently to ensure quality control. Self-designed forms were used for the data extraction in accordance with Cochrane guidelines.
If more trials become available in the future, the heterogeneity between trial results will be tested. Such tests will be subjective, by clinical judgement of differences in patient populations, interventions and outcome assessments, and objective, using appropriate statistical tests. Depending on the results of the heterogeneity assessments, part of the outcomes may be pooled statistically using relevant techniques.
Description of studies
Only one trial (Keisewetter 1993) was identified that fulfilled the criteria for inclusion in the review. Summary details of this trial are given in the 'Characteristics of included studies' table. The trial was relatively small with only 80 patients being randomised and 16 of these did not show sufficient compliance. The duration of the trial was 12 weeks. Further details were requested from the principal author, but no reply was received.
One trial (Koscielny 1999) was excluded because it only measured arteriosclerotic effects and not clinical symptoms. In addition, the subject population was described as 'probationers', and it was not clear if these were healthy volunteers or people with pre-existing disease. Two trials (Larijani 2013; Kieswetter 1997) were excluded because they did not include objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing) or subjective measures (e.g. symptom progression).
Risk of bias in included studies
The one included study (Keisewetter 1993) was randomised, double-blinded and placebo-controlled. There was no mention of the method of randomisation, nor the concealment of allocation (score B). Inclusion and exclusion criteria were adequate, but the trial was of short duration (only 12 weeks). No intention-to-treat analysis was used for the sixteen patients who did not complete the study.
Effects of interventions
The weighted mean difference and a fixed-effect model were used to test the significance of the results. The mean difference between the two groups at the end of treatment was analysed rather than the mean change within the two groups before and after treatment. After twelve weeks of treatment, pain-free walking distance increased from 161 to 207 metres in the garlic group and from 172 to 203 metres in the placebo group. There was no difference in change of systolic or diastolic blood pressure, heart rate, ankle and brachial pressures. No severe side effects were observed but nine patients taking garlic (28%) and four patients taking placebo complained of a noticeable garlic smell (12%). No studies were found comparing dried garlic with non-powder preparations.
The only included study was small and of short duration (12 weeks). Although no statistically significant improvement was found overall, the authors of the trial report that there was a significant increase in walking distance, but this only occurred in the last weeks of therapy. Peripheral arterial occlusive disease is a chronic condition, and any subjective or objective improvement in outcomes would require longer term therapy and follow up.
Implications for practice
One small trial of short duration found no statistically significant effect on walking distance. Thus, at this stage, garlic as a therapy for the treatment of peripheral arterial occlusive disease cannot be recommended.
Implications for research
Further trials of garlic therapy for the treatment of peripheral arterial occlusive disease are required to determine its effectiveness. These trials should be large and of reasonable duration.
We would like to thank Claire Allen (Consumer Representative, Complementary & Alternative Medicine Field) for her very useful comments on the review. We would also like to thank the Cochrane Consumer Network for supplying the Plain Language Summary.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Index terms
Appendix 1. 2013 CENTRAL search strategy
Last assessed as up-to-date: 16 January 2013.
Protocol first published: Issue 2, 1996
Review first published: Issue 3, 1997
Contributions of authors
Ruth Jepson: selected trials for inclusion; sought additional information from the principal investigators of all trials; assessed trials for quality; extracted data; wrote text; revised review (April 2003).
Jos Kleijnen: assessed trials for quality; extracted data.
Gillian Leng: resolved disagreements between RJ and JK regarding trial quality.
The Peripheral Vascular Diseases Review Group assisted with searching for trials for this review.
Declarations of interest
JK reports that Kleijnen Systematic Reviews Ltd has received project funding from various pharmaceutical companies for work in unrelated areas.
Sources of support
- No sources of support supplied
- Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.The PVD Group editorial base is supported by the Chief Scientist Office.
Medical Subject Headings (MeSH)
MeSH check words
Adult; Aged; Female; Humans; Male; Middle Aged