Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK
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Abstract |
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Methods: Four electronic databases were searched for controlled clinical trials of antibacterial herbal medicines. Data were extracted and validated in a standardized fashion, according to predefined criteria, by two independent reviewers.
Results: Seven clinical trials met our inclusion criteria. Four of these studies were randomized. Three trials of garlic and cinnamon treatments for Helicobacter pylori infections reported no significant effect. Bacterial infections of skin were treated in four trials. Positive results were reported for an ointment containing tea leaf extract in impetigo contagiosa infections. Two trials of tea tree oil preparations used for acne and methicillin-resistant Staphylococcus aureus, and one trial of Ocimum gratissimum oil for acne, reported results equivalent to conventional treatments.
Conclusions: Few controlled clinical trials have been published and most are methodologically weak. The clinical efficacy of none of the herbal medicines has so far been demonstrated beyond doubt. This area seems to merit further study through rigorous clinical trials.
Keywords: herbal medicines, antibacterial, clinical trials
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Introduction |
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Materials and methods |
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Results |
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Three trials were found that tested the efficacy of herbal products for the eradication of H. pylori; two tested different preparations of garlic (Allium sativum). A group of 20 H. pylori-infected patients suffering from dyspeptic complaints for >2 months were recruited by Aydin et al.2 A 2 week treatment with capsules containing an oil macerate of garlic (275 mg, three times a day) was compared with the combination of garlic with omeprazole (20 mg, twice a day) for the eradication of H. pylori. All subjects underwent endoscopy before and 1 month after the end of treatment, and the presence of H. pylori in biopsy specimens was confirmed by the urease test and by microscopy. Symptom scores and degree of gastritis, as judged by histological examination, were recorded pre- and post-treatment. Neither intervention resulted in the elimination of the organism, change in the severity of gastritis or a significant change in symptom scores (9.2 ± 1.55 versus 8.7 ± 1.70 in the garlic oil group, 9.0 ± 1.49 versus 8.5 ± 1.51 in the garlic oil plus omeprazole group). The authors considered that low levels of the antibacterial component allicin in the garlic capsules might account for the lack of effect. This trial has obvious weaknesses: it was not randomized, probably not patient-blind and its sample size was small.
Extracts of fresh garlic and capsaicin-containing peppers can inhibit H. pylori in vitro and were tested for their ability to inhibit the bacterium in vivo in a crossover trial involving 12 individuals infected with H. pylori.3 Test substances were included in morning, noon and evening, Mexican-style meals. Subjects participated in a minimum of 3 trial days (negative and positive controls and one experimental ingredient). At least 2 days elapsed between test substances, with bismuth always being the last intervention tested to preclude lasting anti-H. pylori effects. During each test meal participants received one intervention: garlic (10 freshly sliced cloves), capsaicin (six freshly sliced jalapeno peppers), two tablets of bismuth subsalicylate (Pepto-Bismol, positive control) or no additions (negative control). The urea breath test was performed before the first meal of the day, before the evening meal and the morning after each test day. The results were used to evaluate the effectiveness of the therapies. Ten subjects received garlic, six received jalapenos and 11 received bismuth. Neither garlic nor jalapenos had any effect on urease levels (median urease activity pre- and post-garlic 28.5 versus 39.8 and jalapenos 43.7 versus 46.6; P > 0.8) but there was a marked reduction after ingestion of bismuth (55.8 versus 14.3; P < 0.001). Two patients experienced nausea and diarrhoea graded as severe after eating the jalapenos and 70% of those eating garlic complained of taste disturbance and body odour. This study suffered from lack of randomization and small sample size.
Nir et al.4 investigated the effects of treatment with an extract of cinnamon (Cinnamonum cassia) in 23 patients who were undergoing gastroscopy and had a positive urea breath test. Thirty-two patients were randomly allocated in a 2:1 ratio to the study and control groups but only 23 could be included in the final analysis. Fifteen received 80 mg/day cinnamon and eight received placebo for 4 weeks. Breath tests were repeated at the end of the trial period. There were some increased and some decreased urea breath test values in both groups, but overall mean values (pre- and post-cinnamon treatment 22.1 versus 24.4, placebo 23.9 versus 25.9) showed no significant changes. This trial was well designed but its sample size was small and therefore the possibility of a type II error cannot be excluded.
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Staphylococcus aureus and Streptococcus pyogenes infections |
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Strains of S. aureus and Streptococcus pyogenes are the causative agents of the painful and unsightly skin condition impetigo contagiosa. Sharquie et al.6 tested in vitro antibacterial properties of crude preparations of black tea (Thea assamica) and proceeded to a clinical trial in 104 patients with impetigo contagiosa. Tea extracts were incorporated in an aqueous lotion at a concentration of 1% (Group 1) and a vaseline base at a concentration of 5% (Group 2), and these preparations were applied at least three or four times a day. Cure rates in these groups were compared with cure rates in groups given framycetin and gramicidin ointment (Group 3) or oral cefalixin (Group 4). The 5% tea extract was as effective as antibiotic treatments (Groups 24 cure rates 81.3%, 72.2% and 78.6%, respectively). The cure rate in Group1 was 37.5%. Even though the total sample size of this trial seems large, the patient numbers in each treatment arm were low. Moreover, this study suffered from the fact that it was not randomized.
Acne
A single-blind randomized clinical trial (RCT) compared the use of 5% TTO gel with 5% benzoyl peroxide lotion for the treatment of mild to moderate acne in a group of 124 patients.7 Numbers of inflamed and non-inflamed lesions were counted at baseline and at monthly intervals for 3 months and both treatments were effective, although improvements were slower in the TTO group. There was a significantly greater reduction in inflamed lesions in the benzoyl peroxide group at all three follow-up visits. Skin discomfort during treatment was reported less frequently in the TTO group than in those using benzoyl peroxide (44% versus 79%). Without a placebo group it is difficult to decide whether this study demonstrates the presence or absence of a treatment effect and it may also have lacked statistical power to test equivalence between the two therapies.
A recent study tested a range of concentrations of Ocimum gratissimum oil in comparison with 10% benzoyl peroxide and a placebo, over a period of 4 weeks, for the reduction of acne lesions in a population consisting mainly of students.8 O. gratissimum oil was incorporated at concentrations of 0.5%, 1%, 2% and 5% v/v in four different bases (polysorbate 80, cetomacrogol, petrolatum and alcohol) resulting in 16 parallel experimental groups. The number of lesions were counted daily by investigators throughout the test period and the time taken to achieve a 50% reduction relative to pre-treatment was noted for each subject. Preparations containing 2% and 5% Ocimum oil in alcohol and 5% in cetomacrogol were significantly more active than benzoyl peroxide (P < 0.05), while 2% oil in cetomacrogol had similar activity to the reference product. The most active 5% preparations produced skin irritation but the authors considered a 2% preparation in cetomacrogol to be suitable for the management of acne. The sample size of the individual treatment groups was too small to exclude a type II error.
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Discussion |
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Although our search strategy was comprehensive, we cannot be sure that all clinical trials were located. Herbal medicine research is sometimes published in journals not readily accessible through electronic databases and negative trials may not be published at all. It might have been anticipated that trials of cranberry extracts would have been located since it has been used for decades in the management of urinary tract infection. Although a number of studies have examined the use of cranberry for prevention of recurrences of urinary tract infections,9 there are no published clinical trials of its use for treatment of infections10 and it therefore did not meet the inclusion criteria of this review.
Most of the clinical trials located had few participants. Herbal therapies were reported as being as effective as conventional treatments in two trials5,7 and one of the two herbal preparations used in a third trial was as efficacious as two conventional antibiotic regimens.6 The results imply that an O. gratissimum oil preparation is a promising treatment for acne.8 It was as effective as benzoyl peroxide but described as having an unpleasant odour that may, of course, render it less acceptable to patients.
H. pylori infection is common even in asymptomatic individuals and has been shown to be a risk factor for gastric cancer.11 Eradication of the organism can be difficult to achieve with conventional antibiotic therapies, requiring combinations of antibiotics, proton pump inhibitors and bismuth preparations.12 Moreover, adverse effects are regularly associated with these conventional treatments.11
Garlic is one of the most extensively researched medicinal plants.13 Its antibacterial action depends on allicin and is thought to be due to multiple inhibitory effects on various thiol-dependent enzymatic systems.14 Allicin is formed catalytically by crushing raw garlic or adding water to dried garlic, when the enzyme allicinase comes into contact with allicin. Steam distillation of mashed garlic produces garlic oil containing methyl and allyl sulphides of allicin, having the practical advantage of being more stable than allicin itself.
Two controlled trials of garlic preparations used to eradicate H. pylori infection recorded failure.2,3 A further two small trials15,16 without control groups (thus not meeting inclusion criteria of this review) similarly reported no significant results although the garlic preparations used were different in all four trials. Individual constituents of garlic oil and garlic powder have shown a range of potencies when tested in vitro against human enteric bacteria including H. pylori.17,18 Analysis of the herbal preparations used in clinical trials was reported and discussed by McNulty et al.,16 who suggested that active ingredients were at low levels or absent in the preparations used in trials published by Ernst15 and Aydin et al.2 Although the steam-distilled garlic oil preparation used in her own pilot trial had high levels of allicin sulphides, it also proved ineffective. It is possible that an effective treatment might be produced by optimizing the active antibacterial content of preparations and/or judicious use of a combination of conventional and herbal therapies. Garlic and omeprazole have demonstrated synergic properties when tested in vitro against some strains of H. pylori19,20 and the fact that their concurrent use was not effective in the trial reported by Aydin et al.2 may be due to low levels of active garlic components.
Cinnamon extracts in vitro exerted an inhibitory effect on the growth and urease activity of a number of strains of H. pylori21 and encouraged Nir et al.4 to conduct a clinical trial. At the concentration chosen the extract was ineffective in vivo and the authors suggested the possibility that eradication of the organism might be achieved using higher cinnamon concentrations or a regimen combining antibiotic and herbal therapy.
TTO products are widely used as topical treatments by the general public and have proved as effective as conventional treatments for the control of skin bacteria involved in acne7 and of MRSA in a hospital setting.5 Recent research suggests that TTO and its components compromise cytoplasmic membranes of S. aureus,22 weakening the cells ability to withstand the effects of other cytocidal agents. The public perception and potentially devastating results of uncontrolled MRSA spread in hospitals make it a prime target for a new strategy for eradication, and TTO could have a contribution to make in that context. RCTs of TTO have recently been reviewed and the authors concluded that, while it may prove useful as a topical antimicrobial, evidence from well-designed RCTs was lacking.23
A black tea leaf extract, presumed to derive its antibacterial effect from tannins and catechins, demonstrated results equivalent to antibiotic treatments for curing impetigo contagiosa.6 This simple and inexpensive alternative to conventional treatment may be worthy of further rigorous investigation.
In conclusion, the evidence summarized above tentatively suggests possible benefits from some herbal preparations with antibacterial activity. Further large-scale, well-designed clinical trials are required to provide more conclusive proof of their efficacy.
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Acknowledgements |
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Footnotes |
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References |
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2 . Aydin, A., Ersoz, G., Tekesin, O., Akcicek, E., Tuncyurek, M. & Batur, Y. (1997). Does garlic oil have a role in the treatment of Helicobacter pylori infection? Turkish Journal of Gastroenterology 8, 1814.
3 . Graham, D. Y., Anderson, S.-Y. & Lang, T. (1994). Garlic or jalapeno peppers for the treatment of Helicobacter pylori infection. American Journal of Gastroenterology 94, 12002.[CrossRef]
4 . Nir, Y., Potasman, I., Stermer, E., Tabak, M. & Neeman, I. (2000). Controlled trial of the effect of cinnamon extract on Helicobacter pylori. Helicobacter 5, 947.[CrossRef][ISI][Medline]
5 . Caelli, M., Porteous, J., Carson, C. F., Heller, R. & Riley, T. V. (2000). Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphylococcus aureus. Journal of Hospital Infection 46, 2367.[CrossRef][ISI][Medline]
6 . Sharquie, K. E., Al-Turfi, I. A. & Al-Salloum, S. M. (2000). The antibacterial activity of tea in vitro and in vivo (in patients with impetigo contagiosa). Journal of Dermatology 27, 70610.[Medline]
7 . Bassett, I. B., Pannowitz, D. L. & Barnetson, R. S. (1990). A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Medical Journal of Australia 153, 4558.[ISI][Medline]
8 . Orafidiya, L. O., Agbani, E. O., Oyedele, A. O., Babalola, O. O. & Onayemi, O. (2002). Preliminary clinical tests on topical preparations of Ocimum gratissimum Linn leaf essential oil for the treatment of acne vulgaris. Clinical Drug Investigations 22, 3139.
9 . Jepson, R. G., Mihaljevic, L. & Craig, J. (2002). Cranberries for preventing urinary tract infections. (Cochrane Rewiew). In The Cochrane Library, Issue 4, 2002. Update Software, Oxford.
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