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Focus Alternat Complement Ther©2005 Pharmaceutical Press

Home > FACT contents > Volume 12 2007 > Volume 12:3 September 2007 > Focus

Focus Altern Complement Ther 2007; 12: 162–6

Efficacy and safety of Allium sativum (garlic)

Angelo A Izzo

Keywords

  • Adverse effects
  • Allium sativum
  • garlic
  • herbal medicine
  • herb–drug interaction
  • phytopharmacovigilance

Introduction

Allium sativum (garlic) is among the oldest of all cultivated plants and is now popular for both culinary and medicinal purposes. It has been used to treat infections, wounds, diarrhoea, rheumatism, heart disease, diabetes and many other disorders.1–5 It is also widely promoted to reduce abnormal cholesterol and blood pressure levels.6,7 This article focuses on the clinical efficacy and safety of A. sativum.

Efficacy

A. sativum has been clinically evaluated for a number of conditions, including hypertension, hypercholesterolaemia, intermittent claudication, diabetes, rheumatoid arthritis and the common cold; for the prevention of arteriosclerosis and cancer; and as an insect repellent. Systematic reviews are available on its possible antilipidaemic, antihypertensive, antithrombotic and chemo-preventive effects.

Lipid-lowering effect

The ability to lower total serum cholesterol levels is the most researched property of A. sativum. Stevinson and colleagues found 39 clinical trials in the literature dealing with the use A. sativum to treat hypercholesterolaemia.8 The quality of the studies was generally good. Thirteen of these trials (n = 796 persons with baseline values of total cholesterol of about 220 mg/dl) provided data suitable for statistical pooling and thus were included in a meta-analysis of double-blind, placebo-controlled RCTs. Most of the trials (n=10) used a standardised A. sativum powder (Kwai) at daily doses ranging from 600 to 900 mg (generally 900 mg). In other studies, essential oil (0.25 mg/kg body mass/day), spray-dried powder (400 mg/day) and steam-distilled oil (10 mg/day) were used. Duration of the trials ranged from 8 to 20 weeks. A. sativum reduced total cholesterol levels from baseline significantly more than placebo; the weighted mean difference was −15.7 mg/dl (95% CI, −25.6 to −5.7), equivalent to a 5.8% reduction in total cholesterol levels. Six diet-controlled trials with the highest scores for methodological quality revealed a non-significant difference between A. sativum and placebo groups; the weighted mean difference was −4.3 mg/dl. Although A. sativum was superior to placebo, the authors of this systematic review concluded that the size of the A. sativum effect is modest. There is also evidence that the effect of A. sativum on blood lipids may depend on the duration of treatment. Meta-analyses of placebo-controlled RCTs showed that A. sativum preparations led to small reductions in the total cholesterol level at 1 month (average reduction 7.2 mg/dl) and at 3 months (average reduction 17.1 mg/dl), but not at 6 months. Changes in LDL-C levels and triglyceride levels paralleled total cholesterol level results; no statistically significant changes in HDL-C levels were observed.7 Finally, a more recent systematic review found A. sativum to be effective in six of ten RCTs.9 The average drop in total cholesterol was 9.9%, LDL-C 11.4% and triglycerides 9.9%.

Overall, the use of A. sativum for hypercholesterolaemia is of questionable value.

Hypertension

The effect of A. sativum on hypertension has been summarised.7 Of 30 trials measuring blood pressure outcomes, only seven were placebo-controlled RCTs investigating the effect of A. sativum as a monopreparation. Although several trials reported significant reductions in blood pressure among subjects given A. sativum (within-group comparisons), only three demonstrated statistically significant reductions in diastolic blood pressure (range 2–7%), and one in systolic blood pressure (approximately 3%) between persons given A. sativum and those given placebo. An earlier meta-analysis also confirmed that the evidence is insufficient for treatment recommendations.10

Pre-eclampsia is a hypertensive disorder that occurs during the second half of pregnancy. A recent systematic review11 retrieved one trial (100 women) of uncertain quality, which compared A. sativum (800 mg Garlet/day) with placebo. The participants were women at moderate risk of pre-eclampsia, as determined by a positive roll-over test. Another study was excluded as 29% of women were lost to follow-up. There was no clear difference between the A. sativum and control groups in the risk of developing gestational hypertension. The authors concluded that there is insufficient evidence to recommend increased A. sativum intake for preventing pre-eclampsia and its complications.

Antithrombotic effects

Ackermann and colleagues retrieved 10 trials assessing the effectiveness of A. sativum on potential prothrombotic risk factors.7 Of six trials measuring effects on spontaneous platelet aggregation, five provided significant inhibitory effects compared to placebo in platelet aggregation.7 A. sativum had a positive response in the inhibition of platelet aggregation in both healthy subjects and subjects with cardiovascular disease.6 Mixed effects on fibrinolytic activity and plasma viscosity were reported, while no trials assessing serum fibrinogen levels or serum homocysteine levels reported significant results.7

Prevention of atherosclerosis

The role of A. sativum in treating atherosclerotic cardiovascular disease has been postulated for many years, but until recently few studies on A. sativum’s ability to inhibit the atherosclerotic process have been reported.4,12 A. sativum intake has been shown to reduce the volume of existing atherosclerotic plaques (5–18% compared to placebo) in 152 patients after 4–18 months of treatment.13 Another study demonstrated that chronic A. sativum powder intake (900 mg/day of A. sativum powder for 4 years) delayed age-related increases in aortic stiffness in older, healthy adults (n = 101) who took more than 300 mg/day of standardised A. sativum powder.14 More recently, a placebo-controlled, double-blind pilot RCT (n = 19 coronary high-risk subjects) evaluating coronary artery calcification and the effect of 1-year aged A. sativum extract therapy in a group of patients who were also on statin therapy, suggested incremental benefits.12

Other cardiovascular protective properties

Rahman and Lowe6 found a reduction in oxidative stress in five out of seven retrieved studies. Other cardio-protective effects of A. sativum in humans include decrease in unstable angina and increase in the elastic property of blood vessels.6 However, the number of trials conducted within this area is limited.6 Ackermann and colleagues7 found significant reductions in serum glucose (in non-diabetics) in only one of 12 retrieved trials that assessed the effect of A. sativum on glucose levels.7 Finally, two trials showed improvement in pain-free walking distance in subjects with lower extremity peripheral vascular disease (intermittent claudication) treated with A. sativum.6

Chemoprevention

Diet is thought to be one of the most important contributing factors to cancer risk.15 A recent systematic review summarised the efficacy and safety of herbal medicines and vegetables in cancer prevention.16 Of the 14 epidemiological studies identified on A. sativum, six (range n = 272–41 837, five case-control studies and one prospective cohort study) reported dietary intake of A. sativum to be associated with significant, dose-dependent reductions in risk for specific cancers, including colorectal regions (two studies), prostate (one study) and stomach cancer (three studies). Significant results were achieved with intake frequencies ranging from once a month to two or more times per week. However, eight case-control and cohort studies reported no significant risk reduction of cancer of the gastrointestinal tract (six studies), lung (one study) and breast (one study). The authors cautiously conclude that A. sativum intake as part of the diet might be useful in preventing some types of cancer; analysis of the trials revealed a promising (although not compelling) chemopreventive effect for prostate and stomach cancer. Recent double-blind RCTs showed that aged A. sativum extract may exert preventive and therapeutic effects on colorectal adenomas,17 and improve natural killer cell activity in patients with advanced cancer of the gastrointestinal tract.18 By contrast, aged A. sativum extract did not modify the prevalence of precancerous gastric lesions.19

Other clinical studies

A clinical study revealed that a topical 1% ajoene cream was effective for superficial tinea infections;20 another trial showed that topical application of A. sativum paste was effective in suppressing clinical signs of oral candi-diasis (n = 56 patients).21 In an RCT of 20 Helicobacter pylori-positive dyspeptic patients, A. sativum oil capsules had no effect on symptoms, histological gastritis grade, or H. pylori density.22 An RCT (n = 146) implied that high-dose A. sativum consumption reduces the frequency of tick bites in a tick-endemic area.23 However, a preliminary double-blind, placebo-controlled trial of A. sativum as a mosquito repellent failed to show positive results.24 Finally, some trials have generated preliminary encouraging findings of A. sativum for the prevention of common cold25 and as a symptomatic treatment for rheumatoid arthritis.26

Safety

A. sativum appears to be generally safe. Controlled clinical trials as well as observational studies have consistently shown that A. sativum breath and body odour are the most common, and well-documented, complaints associated with A. sativum intake.8,27 Allergic reactions may also occur. An observational study showed that a regimen of 3 × 300 mg/day A. sativum powder, taken in the form of coated tablets, caused an allergic reaction in 1.1% of users.27 Published reports indicated clinical cases of allergic contact dermatitis, generalised urticaria, angioedema, pemphigus and anaphylaxis after intake of A. sativum as a food or as a medicine.28–33 Photoallergic reactions have also been reported.34

A. sativum has long been recognised as an occupational hazard, a possibility highlighted by a number of observational studies in occupational allergic patients,35,36 as well as case reports and case series.3 Contact dermatitis, particularly affecting the fingertips, is a well-recognised presentation of A. sativum occupational allergy.3 Other adverse events associated with occupational exposure (contact or inhalation) to A. sativum include asthma, dyspnoea, cough, rhinitis and rhinoconjunctivitis.3,37.

A. sativum in its fresh crushed-clove form is a potent irritant and, under occlusive dressings, this potency is enhanced.38,39 A. sativum irritants include sulphur compounds such as isothiocyanates. The possibility that A. sativum may cause irritant (non-allergic) contact dermatitis (known as A. sativum burns) has been highlighted by a number of case reports/case series, both in infants and in adults.40–44 The cases involved the feet, wrists, hands, trunk, breast and forehead. The A. sativum was applied to treat asthma, skin lesions, pain and fever, and in some instances for self-mutilation, in order to avoid military duty or without a precise and rational motive.40–44 In all cases, the burns were successfully managed with conservative treatment alone.

There is also evidence that some of the antiplatelet activity of A. sativum might be irreversible and thus it has been suggested that patients cease ingestion at least 7 days before surgery.45 A few case reports have highlighted the possibility that A. sativum may increase the risk of bleeding, particularly in patients undergoing surgery. These include spontaneous spinal epidural haema-toma causing paraplegia,46 increase in the clotting time before a cosmetic surgery,47 ‘bloody’ resection for prostatic benign hyperplasia,48 and bilateral retrobulbar haemorrhage with elevated intraocular pressure during strabismus surgery.49

There are few published studies on the effect of A. sativum during pregnancy. A single-blind trial50 that compared A. sativum (n = 50) with placebo (n = 50) for the prevention of pre-eclampsia during the third trimester of pregnancy found no significant differences in reported side-effects, except for A. sativum odour, which was reported to be more likely in the A. sativum group (34%) than in the placebo group (4%). Eight subjects claimed a slight feeling of nausea in the A. sativum group compared to two subjects in the placebo group. The percentage of Caesarean section was 62% in the A. sativum group and 46% in the placebo group. No perinatal morbidity and mortality in the two groups was observed.50 A. sativum ingestion (i) by pregnant women significantly alters the odour of their amniotic fluid,51 and (ii) by nursing mothers modifies their infant’s behaviours during breastfeeding.52

There is evidence that taking A. sativum can result in pharmacokinetic or pharmacodynamic interactions that might represent a potential risk to patients taking conventional medicines, particularly those under anticoagulant or antiretroviral therapy.53 Two cases of increased international normalised ratio (INR) in patients previously stabilised on warfarin have been reported.54 An increase of INR has also been described in a subject taking the anticoagulant drug fluindione.55 These reports, however, contained inadequate information to assess the likelihood of an interaction. Recently, it has been suggested that aged A. sativum extract is relatively safe and poses no serious haemorrhagic risk for closely monitored patients on warfarin therapy.56 Clinical studies reported significant decline in the plasma concentrations of the protease inhibitor saquinavir (but not ritonavir) in healthy volunteers after repeated administration of A. sativum.57,58 The precise mechanism of this interaction is not known. Although A. sativum may increase cytochrome P450 in animals, human studies have shown that it has little or no effect on drug metabolism.59,60 Also, a poorly described case report suggested that A. sativum might increase the antidiabetic effect of chlorpropamide.61 Finally, a clinical trial suggested that A. sativum changes some pharmacokinetic variables of paracetamol (acetaminophen) after 1–3 months of treatment, but it is very unlikely that these pharmacokinetic changes are of major clinical significance.62

Conclusions

A. sativum is mainly promoted to lower plasma cholesterol, as an antihypertensive and for the prevention of atherosclerosis. However, the clinical evidence is far from compelling; effects are generally small or of limited clinical significance. The regular intake of A. sativum might have some protective effects against stomach and prostate cancer, but in-depth and appropriate studies are required to confirm this. A. sativum appears to be generally safe. Complaints that have been documented in clinical trials include breath/body odour and mild gastrointestinal symptoms. Allergic reactions may also occur. Application of A. sativum on the skin may cause irritant dermatitis, known as A. sativum burns. Finally, A. sativum may interact with anticoagulant/antiplatelet and anti-AIDS drugs.

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Angelo A Izzo is an Associate Professor of Phytotherapy and Pharmacognosy at the School of Pharmacy of Naples, University of Naples Federico II, via D Montesano 49, 80131 Naples, Italy. He is also a member of the international editorial board of FACT. E-mail: aaizzo@unina.it
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