|Grade||Level of Evidence|
|A||Multiple double-blind, controlled clinical trials.|
|B||1 double-blind, controlled clinical trial.|
|C||At least 1 controlled or comparative clinical trial.|
|D||Uncontrolled, observational, animal or in-vitro studies only.|
|Grade||Effect||Size of Effect||Comments|
More effective than placebo in reducing acne and as effective as 5% benzoyl peroxide in reducing non-inflamed lesions. Less effective and slower than 5% benzoyl peroxide in decreasing inflamed lesions.
10 µl/ml tea tree oil was as effective as 30 mM butylated hydroxytoluene at scavenging free radicals and inhibiting the oxidation of hexanal.
Only 1 case report in which a paediatric patient successfully removed warts on her right middle finger using topical tea tree oil.
Does not inhibit wound healing, but the evidence of it actually aiding wound healing is weak.
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Table of contents:
- 1. Sources
- 2. Bioavailability
- 3. Effects on the skin
- 4. Side Effects
Tea tree oil is a clear to pale yellow essential oil distilled from the foliage of Melaleuca alternifolia, a hardwood tree native to the northeastern area of New South Wales, Australia. The plant has also been cultivated in other states, including Queensland and Western Australia, as well as in other countries.
Tea tree oil is a mixture of almost 100 compounds, but the most abundant are terpinen-4-ol (40.1%), γ-terpinene (23.0%), α-terpinene (10.4%) and 1,8-cineole, also known as eucalyptol (5.1%). 6 distinct oil phenotypes have been identified to date, of which one is dominated by terpinen-4-ol, one by terpinolene and the remaining four by eucalyptol. Although all chemotypes are present throughout the distribution range of Melaleuca alternifolia, there is a connection between the different oil types and geographic location. Terpinen-4-ol types predominate in and around the Bungawalbin basin in northern New South Wales, eucalyptol types predominate slightly further south around Grafton, and terpinolene types predominate in southern Queensland.
The terpinen-4-ol chemotype is the one used for commercial tea tree oil production. About 400 tons of tea tree oil are produced per annum. It is included as an ingredient in skin care and other over-the-counter products such as soaps, bath additives, shampoos and conditioners, mostly at concentrations of 2% and below, except in nail care products where it is typically included at a concentration of 20%. Undiluted tea tree oils are also available.
Several studies have evaluated the uptake of tea tree oil and some of its components (terpinen-4-ol, eucalyptol, linalool, α-pinene and β-pinene) into the skin. All the studied components are known to be absorbed in the viable epidermis and dermis, with terpinen-4-ol showing the fastest penetration. Terpinen-4-ol in 5% tea tree oil formulations has also been shown to accumulate in the follicles of bovine udder skin as well as to be retained in human skin tissue following topical application.
The type of dermatological vehicle employed affects the absorption kinetics of tea tree oil compounds. Terpinen-4-ol and linalool for instance penetrate the skin better from a hydrogel than from oily solutions or oil-in-water emulsions. A semisolid oil-in-water emulsion containing 5% tea tree oil, however, led to greater flux across the skin than similar preparations in white petrolatum or an ambiphilic cream.
Excipients too can influence the cutaneous uptake of tea tree oil, with oleic acid in particular observed to enhance the absorption of terpinen-4-ol by perturbing the stratum corneum barrier, whereas isopropyl myristate, polyethylene glycol 400 and Transcutol only caused a weak enhancement effect.
The penetration of tea tree oil components through human skin appears limited -- only 1-2% and 2-4% of the dose respectively penetrated into or through human epidermis when a 20% tea tree oil solution and pure tea tree oil were applied, though partial occlusion of the application site did increase the epidermal penetration of pure tea tree oil to approximately 7%. Tea tree oil patches prepared using the methacrylic copolymer Eudragit E100 have also demonstrated high retention and low permeation of terpinen-4-ol.
Unabsorbed tea tree oil is probably removed from the skin through evaporation. In an experiment on filter paper, 98% of the oil evaporated within 4 hours.
3. Effects on the skin
3.1 Antioxidant effect
Tea tree oil contains several inherent antioxidants such as α-terpinene, γ-terpinene and α-terpinolene. In the 2,2-diphenyl-1-picrylhydrazyl assay, 10 µl/ml tea tree oil in methanol showed approximately 80% free radical scavenging activity, and 200 µl/ml tea tree oil exhibited 60% inhibition against the oxidation of hexanal to hexanoic acid over 30 days. These results were equivalent to the activities of 30 mM butylated hydroxytoluene, an antioxidant used in small amounts as a food additive. Washing with 5% tea tree oil has been shown to be effective in removing MRSA from the skin.
3.2 Antimicrobial activity
Tea tree oil inhibits the growth of a number of bacterial species found on the skin, including S. aureus, S. epidermidis, P. aeruginosa and P. acnes by compromising the structural and functional integrity of bacterial membranes, leading to the loss of intracellular material, an inability to maintain homeostasis and inhibition of respiration.
A range of yeasts, dermatophytes and other filamentous fungi are susceptible to tea tree oil, which has been demonstrated to alter the permeability of fungal membranes, affect sporulation and inhibit the formation of germ tubes. As a consequence, tea tree oil has been used to treat athlete's foot and onchomyosis.
Tea tree oil also possesses antiviral and antiprotozoal activity. It inhibits the replication of herpes simplex virus (HSV) and is virucidal against 2 HSV subtypes in viral suspension tests. It also interferes with the replication of influenza virus, and inhibits their entry into host cells. In addition, it is also toxic to trypanosomes such as T. brucei, T. evansi and L. major.
Hence, it is possible to use tea tree oil as a component of preservative systems. The combination of 0.5% tea tree oil + 0.5% lavender oil can reduce the level of synthetic preservative used in body milks by 8.5 times (from 0.85% to 0.1%), while maintaining the same antimicrobial efficacy.
However, it has also been observed that the antimicrobial activity of essential oils decreases in cosmetic formulations. This is thought to result from their affinity to the oil phase of the formulation, which limits their accessibility in the aqueous phase. The addition of solubilizers, organic compounds with both hydrophobic and hydrophilic portions, can counter this reduction. For instance, the introduction of the solubilizer polysorbate 80 to a soft body balm containing 0.5% tea tree oil led to a considerable increase in the bacteriostatic activity of the formulation.
3.3 Acaricidal activity
Eyelid scrubs or massage with tea tree oil effectively kills Demodex mites, the most common ectoparasite found in human skin. The most active ingredient in tea tree oil responsible for this effect is terpinen-4-ol, which has been observed to exert a killing effect at a concentration of just 1%. Tea tree oil has also been shown to kill Sarcoptes scabiei, the mite that causes scabies, and Ixodes ricinus, a species of pathogen-bearing ticks, in vitro.
3.4 Acne treatment
3 compounds in tea tree oil, namely α-terpineol, terpinen-4-ol and α-pinene inhibit P. acnes, which is believed to be involved in the pathogenesis of acne. Moreover, tea tree oil appears to accumulate in the follicles, especially in microemulsion and liposomal formulations. This is potentially important as several functions of the sebaceous glands, which are attached to the hair follicles, are also associated with the development of acne.
One of the first rigorous clinical studies on tea tree oil assessed its efficacy in treating acne compared to benzoyl peroxide. The study found that both 5% tea tree oil gel and 5% benzoyl peroxide lotion ameliorated acne by reducing the numbers of inflamed and non-inflamed lesions. Although benzoyl peroxide was better at decreasing inflamed lesions and oiliness and had a faster onset of action, patients treated with tea tree oil experienced fewer side effects.
More recently, a randomized, double-blind and placebo-controlled study published in 2007 found that a 5% tea tree oil gel was 3.55 times and 5.75 times more effective than placebo in decreasing total acne lesion count and acne severity in patients with mild-to-moderate acne vulgaris.
3.5 Anti-inflammatory effect
Tea tree oil has anti-inflammatory properties. It suppresses the production of superoxide anions by human monocytes (but not neutrophils) and the production of inflammatory mediators by human macrophages activated in vitro.
In mice, it has been shown to inhibit histamine-induced edema in the ears and to cause a significant reduction in skin swelling induced by a hapten challenge, and in humans it has also demonstrated an ability to contain histamine-induced skin inflammation.
Because of its known anti-inflammatory properties, tea tree oil has been suggested as a novel potential agent against psoriasis.
3.6 Warts treatment
There has been one case report of tea tree oil successfully treating a paediatric patient with warts on her right middle finger. Tea tree oil was applied topically to the lesions once daily, and complete re-epithelization was achieved after 12 days. This may be due to the antiviral action of tea tree oil, though its activity on the human papilloma virus that causes warts has not yet been shown.
There has however also been a case of allergic contact dermatitis to tea tree oil in a 74-year-old man who used a 1% tea tree oil solution to treat warts.
The proven antimicrobial and anti-inflammatory properties of tea tree oil gives it promise as an adjunctive treatment for wounds, but the quality of the clinical data supporting its efficacy is poor. A case study published in 2011 reported that a topical solution comprising 10% tea tree oil mixed with 90% pumpkin seed oil completely healed 2 nickel-sized wounds caused by a surgical incision for a below-the-knee amputation. An open-label pilot study published that same year found that tea tree oil did not inhibit healing when used in a wound cleansing procedure.
Moreover, another small investigational study published in 2013 compared the healing times of wounds infected with S. aureus with conventional treatment alone versus conventional treatment plus fumes of tea tree oil, and found decreased healing times in all but 1 participant treated with tea tree oil.
Yet despite lowering the subdermal temperature within the skin during treatment, a commercial dressing impregnated with tea tree oil (Burnaid) did not decrease the microflora or improve re-epithelialisation, scar strength, scar depth or scar appearance when applied to a deep dermal contact burn on pig skin. In fact, tea tree oil has even been recommended not to be used on burn wounds, due to its cytotoxicity against human fibroblasts and epithelial cells.
3.8 Other effects and uses
A 5% tea tree oil shampoo was more effective than placebo in a randomized, single-blind trial on 126 patients with mild-to-moderate dandruff. This was thought to be due to its antifungal properties, as dandruff is related to the yeast P. ovale. In another study, an oil spray containing lavender oil + tea tree oil led to a statistically significant reduction from baseline in hirutism total score and hair diameter after 3 months, unlike placebo; however, whether the differences were statistically significant between groups was not reported.
Tea tree oil has displayed an ability to inhibit the growth of multidrug resistant human melanoma cells in vitro by interacting with the plasma membrane and inducing caspase-dependent apoptosis. It had a similar effect in 2 aggressive murine cancer cell lines (AE17 mesothelioma and B16 melanoma), eliciting G1 cell cycle arrest and inducing necrotic cell death coupled with low level apoptotic cell death. These results have been extended by 2 in vivo studies, which showed that topical tea tree oil formulations containing 10% tea tree oil in dimethyl sulphoxide (DMSO) successfully regressed mesotheliomas and retarded the growth of subcutaneous melanomas in mice by causing direct anti-cancer cytotoxicity.
4. Side Effects
4.1 Contact dermatitis
Tea tree oil is a skin sensitizer. In one study, 3 out of 150 panelists (2%) became sensitized to tea tree oil after various concentrations (5%, 25% and 100%) of tea tree oil in different vehicles were applied under occlusive patch testing to healthy skin, though it was not possible to determine which specific concentrations were responsible.
Clinical patch testing has also identified tea tree oil as an occasional skin allergen. Out of 1216 patients patch-tested in a Swiss dermatologic clinic in 1997, 7 (0.6%) had allergic contact dermatitis to tea tree oil. In a Danish dermatology clinic, only 1 out of 377 patients (0.3%) from 2001-2003 showed a positive patch test to 5% and 10% tea tree oil, but an additional 5 (1.3%) had irritant reactions to 5% tea tree oil. A multicenter study conducted by the German Contact Dermatitis Group likewise found positive reactions to 5% tea tree oil in 36 out of 3375 patients (1.1%) from 11 dermatological departments in Germany and Austria. In Australia where tea tree oil originates, a retrospective review of patch test data at the Skin and Cancer Foundation of Victoria over a 4.5 year period identified 41 cases of positive reactions to oxidized tea tree oil out of 2320 people patch-tested, giving a prevalence of 1.8%. More recently, a 2012 paper asserted a prevalence rate of 1.4% among patients referred for patch testing.
These results help account for the numerous case reports in the medical literature about contact dermatitis or contact allergy associated with the use of tea tree oil, especially in the 1990s and early 2000s.
It is not fully understood which of the constituents in tea tree oil are allergenic and induce sensitization, but oxidized tea tree oil has been shown to be 3 times more potent than freshly distilled tea tree oil. Hence, known oxidative degradation products such as ascaridole, 1,2,4-trihydroxymenthane, peroxides and epoxides have been discussed, in addition to other components like terpinolene, α-terpinene, a sesquiterpenoid fraction and limonene.
Curiously, tea tree oil actually appears to attenuate nickel-induced allergic contact hypersensitivity, with one study showing a 40.5% reduction in nickel-induced allergic contact dermatitis. Its mode of action requires further investigation, but has been hypothesized to involve antigen-presenting cells or the antigen-presenting process, as well as vascular changes associated with this response.
4.2 Risk of systemic toxicity
Several incidences of tea tree oil poisoning have occurred due to ingestion of tea tree oil. A 60-year-old man who swallowed half a teaspoonful of tea tree oil developed a dramatic rash accompanied by leukocytosis. In another case, one person lapsed into a 12-hour coma and suffered another 36 hours of disturbances of consciousness after drinking half a cup of pure tea tree oil. There have also been at least 3 reports of tea tree oil poisoning in young children. The first described a 17-month-old boy who ingested <10 ml of tea tree oil developed ataxia and drowsiness. Similarly, a 23-month-old boy became confused and was unable to walk half an hour after ingesting <10 ml of a commercial product containing 100% tea tree oil, though he was asymptomatic within 5 hours. The third report was of a 4-year-old boy who became ataxic within 30 minutes of ingesting a small quantity of tea tree oil, that progressed to unresponsiveness shortly thereafter.
The magnitude of systemic exposure to tea tree oil from cosmetic products is not known due to inadequate dermal absorption studies, but one case of an immediate systemic hypersensitivity reaction including flushing, pruritus, throat constriction and lightheadedness associated with topical application of tea tree oil has been reported.
There have also been many cases of tea tree oil toxicosis in pet dogs and cats from intentional or accidental use of tea tree oil, causing central nervous system depression, paresis, ataxia and muscle tremors.
4.3 Potential carcinogenicity
Tea tree oil contains minor amounts of methyleugenol, a suspected carcinogen. However, no studies that we are aware of have demonstrated any carcinogenic effects of tea tree oil. In fact, several indicate that tea tree oil can combat subcutaneous tumours such as melanoma and mesothelioma.
4.4 Link to gynecomastia
Tea tree oil has been linked to gynecomastia in 2 young males. In vitro experiments subsequently confirmed that tea tree oil as a whole does have estrogenic potency, but because none of the skin-penetrating constituents demonstrated estrogenicity, the relation between topical use of tea tree oil and gynecomastia was considered implausible by the Scientific Committee on Consumer Products in 2008.
4.5 Other side effects
Tea tree oil can be cytotoxic to human fibroblasts and epithelial cells depending on the concentration. It was however not genotoxic in cultures of human lymphocytes, corroborating an earlier study which found no mutagenic potential among a variety of commercially available tea tree oils using the Ames test. The results of another study suggested that high concentrations of tea tree oil applied to the round window of the ear is to some extent ototoxic to the high-frequency region of the cochlea, but that further studies were required to determine if tea tree oil can be safely used in the treatment of ear infections.
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