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# Medical Studies
1 A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne.
Bassett IB, Pannowitz DL, Barnetson RS.
Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, NSW.

Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions. We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower. Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.
2 Tea tree oil: a systematic review of randomized clinical trials.
Ernst E, Huntley A.
Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK. E.Ernst@ex.ac.uk

AIM: Tea tree oil (TTO) is immensely popular for various topical applications. In vitro studies have repeatedly demonstrated that it has antibiotic activity. This article is an attempt to systematically review the evidence from randomised clinical trials for or against effectiveness of external TTO in dermatological conditions. METHODS: Six electronic databases were searched. Methodological quality was assessed by Jadad score. Data were extracted and validated in a standardised fashion by two independent reviewers. RESULTS: Only 4 trials were located. They suggest that TTO may be effective as a treatment of acne and fungal infections. The evidence is promising but by no means compelling. The adverse effects of TTO are usually mild and transient. They mainly consist of allergic reactions. CONCLUSIONS: It is concluded that, so far, there is no compelling evidence to show that TTO is efficacious in any dermatological condition. However, in view of promising findings, TTO deserves to be investigated more closely.
3 Adverse and beneficial effects of plant extracts on skin and skin disorders.
Mantle D, Gok MA, Lennard TW.
Department of Surgery, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU.

Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g. peanut allergy, poison ivy (Toxicodendron) poisoning).
4 Tea tree oil reduces histamine-induced skin inflammation.
Koh KJ, Pearce AL, Marshman G, Finlay-Jones JJ, Hart PH.
Department of Dermatology, Flinders Medical Centre, Bedford Park, South Australia, Australia.

BACKGROUND: Tea tree oil is the essential oil steam-distilled from Melaleuca alternifolia, an Australian native plant. In recent years it has become increasingly popular as an antimicrobial for the treatment of conditions such as tinea pedis and acne. OBJECTIVES: To investigate the anti-inflammatory properties of tea tree oil on histamine-induced weal and flare. METHODS: Twenty-seven volunteers were injected intradermally in each forearm (study and control assigned on an alternating basis) with histamine diphosphate (5 microg in 50 microL). Flare and weal diameters and double skin thickness were measured every 10 min for 1 h to calculate flare area and weal volume. At 20 min, 25 microL of 100% tea tree oil was applied topically to the study forearm of 21 volunteers. For six volunteers, 25 microL paraffin oil was applied instead of tea tree oil. RESULTS: Application of liquid paraffin had no significant effect on histamine-induced weal and flare. There was also no difference in mean flare area between control arms and those on which tea tree oil was applied. However, mean weal volume significantly decreased after tea tree oil application (10 min after tea tree oil application, P = 0.0004, Mann-Whitney U-test). CONCLUSIONS: This is the first study to show experimentally that tea tree oil can reduce histamine-induced skin inflammation.
5 Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials.
Martin KW, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK. karen.martin@pms.ac.uk

OBJECTIVES: Many hundreds of plant extracts have been tested for in vitro antibacterial activity. This review is a critical evaluation of controlled clinical trials of herbal medicines with antibacterial activity. 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.
6 Tea tree oil concentration in follicular casts after topical delivery: determination by high-performance thin layer chromatography using a perfused bovine udder model.
Biju SS, Ahuja A, Khar RK.
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi 110 062, India. bijuss1@hotmail.com

Tea tree oil, a popular antimicrobial agent is recommended for the treatment of acne vulgaris, a disease of the pilosebaceous unit. Tea tree oil formulations (colloidal bed, microemulsion, multiple emulsion, and liposomal dispersion containing 5% w/w tea tree oil) were applied to bovine udder skin. The follicular uptake of tea tree oil upon application was determined by a cyanoacrylate method. Tea tree oil was determined by quantifying terpinen-4-ol content using high-performance thin layer chromatography. The accumulation of tea tree oil in the follicular casts was 0.43 +/- 0.01, 0.41 +/- 0.009, 0.21 +/- 0.006, and 0.16 +/- 0.005 percentage by weight (milligram oil/gram of sebum plug) for microemulsion, liposomal dispersion, multiple emulsion, and colloidal bed, respectively. This is the first study of its kind to quantify tea tree oil concentration in the follicles. Copyright 2004 Wiley-Liss, Inc.
7 The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study.
Enshaieh S, Jooya A, Siadat AH, Iraji F.
Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

BACKGROUND: Finding an effective treatment for acne that is well tolerated by the patients is a challenge. One study has suggested the efficacy of tea tree oil in treatment of the acne vulgaris. AIM: To determine the efficacy of tea tree oil in mild to moderate acne vulgaris. METHODS: This was a randomized double-blind clinical trial performed in 60 patients with mild to moderate acne vulgaris. They were randomly divided into two groups and were treated with tea tree oil gel (n=30) or placebo (n=30). They were followed every 15 days for a period of 45 days. Response to treatment was evaluated by the total acne lesions counting (TLC) and acne severity index (ASI). The data was analyzed statistically using t-test and by SPSS program. RESULTS: There were no significant differences regarding demographic characteristics between the two groups. There was a significant difference between tea tree oil gel and placebo in the improvement of the TLC and also regarding improvement of the ASI. In terms of TLC and ASI, tea tree oil gel was 3.55 times and 5.75 times more effective than placebo respectively. Side-effects with both groups were relatively similar and tolerable. CONCLUSION: Topical 5% tea tree oil is an effective treatment for mild to moderate acne vulgaris.
8 A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne.
Bassett IB, Pannowitz DL, Barnetson RS.
Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, NSW.

Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions. We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower. Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.

9 Antimicrobial effects of tea-tree oil and its major components on Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes.
Raman A, Weir U, Bloomfield SF.
Department of Pharmacy, King's College London, UK.

Major components of two tea-tree oil samples were identified using thin layer and gas-liquid chromatography (TLC and GLC). Using a TLC-bioautographic technique, the tea-tree oils, terpinen-4-ol, alpha-terpineol and alpha-pinene were found to be active against Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes whereas cineole was inactive against these organisms. The MIC values of the three active compounds increased in the order alpha-terpineol < terpinen-4-ol < alpha-pinene for all three micro-organisms. MIC values of the tea-tree oils and terpinen-4-ol were lower for P. acnes than for the two staphylococci. This study supports the use of tea-tree oil in the treatment of acne, and demonstrates that terpinen-4-ol is not the sole active constituent of the oil.

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