Tea Tree Oil for Fungal Infections
By Eric Harvey, PharmD, BCPS, MBA
Native australians have used boiled leaves of Melaleuca alternifolia as a topical anti-infective for hundreds of years. The plant was given its common name, tea tree, following Captain James Cook’s exploration of New South Wales in 1770. During World War II, Australian manufacturers added tea tree oil (TTO) to metal cutting oils as an anti-infective in an attempt to reduce workers’ risk of infection from on-the-job lacerations.1,2
TTO is currently promoted as a treatment for cutaneous fungal infections including tinea pedis and onychomycosis. It also is used to treat acne, prevent bacterial infections, and as a skin disinfectant.1-3
Pharmacology and Mechanism of Action
Terpinen-4-ol is the most abundant (40-60% of total volume) antimicrobial compound in TTO followed by 1,8-cineole and alpha-terpineol. In vitro antimicrobial activity has been documented against many common yeasts and fungi including Candida albicans, other Candida sp., Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, and Malassezia furfur.3,4 Based on in vitro data, topical application of TTO in concentrations of 5% v/v or higher should be adequate to eradicate these organisms from skin surfaces.3-5 TTO also has demonstrated activity against many important gram-positive and gram-negative bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, and Propionibacterium acnes.1,2
Clinical Trials
A randomized, double-blind controlled trial (RDBCT) in 121 patients with symptomatic tinea pedis used tolnaftate 1% cream (Tinaderm®), TTO 10% in sorbolene cream base, or sorbolene cream base (as placebo) bid for four weeks.6 A negative fungal culture excluded 15 patients originally randomized. The mycological cure rate of tolnaftate (85%) was statistically superior to both TTO (30%) and placebo (21%). Symptoms of scaling, itching, inflammation, and burning were individually rated. Symptom scores (0 = absent to 4 = very severe) were summed for each visit; a reduction by 2 points or more in total score was considered symptom improvement. At week 4, 46%, 22%, and 9% of tolnaftate, TTO, and placebo patients, respectively, had both improvement of symptoms and a negative culture; 12%, 43%, and 32% had improvement of symptoms only. Tolnaftate and TTO were both statistically superior to placebo for rate of symptom improvement. One tolnaftate patient reported mild erythema that resolved without treatment interruption; no patients dropped out because of side effects. The relatively high symptom improvement rate in the placebo arm may reflect the impact of routine washing and drying of feet as a condition of study participation. The symptom scoring method used to assess treatment response is neither standardized nor easily replicated. An absolute standard of "complete symptom resolution" would have been more reliable and useful. Level II, major limitations
In another RDBCT, 117 patients with culture-proven toe onychomycosis were treated with 1% clotrimazole solution or 100% TTO bid for six months.7 Outcomes were not statistically different between clotrimazole (n = 53) and TTO (n = 64) as measured by mycological cure rate (clotrimazole 11%, tea tree oil 18%), resolution of symptoms at the end of therapy (61% and 60%, respectively), or resolution of symptoms three months after therapy ended (55% and 56%, respectively). The study had 80% power to detect a difference in cure rate of at least 20%. Four clotrimazole patients and one TTO patient were lost to follow-up. Three clotrimazole patients and five TTO patients reported erythema, irritation, or edema; four dropped out because of adverse effects (their treatment arms were not specified). Symptom status was obtained by a physician’s subjective assessment of "full," "partial," or "no" resolution. Both "full" and "partial" resolution were combined and considered positive results. A more absolute measure of symptom resolution would have been more reliable. The low mycological cure rate reported for treatment with topical clotrimazole lends credence to the suspicion that a systemic antifungal may have been a better active control. Another limitation is the lack of a placebo arm. Level I, major limitations
A case series of patients with a variety of foot conditions has lent support to TTO’s antifungal claims.8 Treatment was not blinded and was given for highly variable durations to treat culture positive tinea pedis or toe onychomycosis. Twelve people used an 8% TTO ointment daily to treat seasonal athlete’s foot. Eight reported resolution of tinea pedis symptoms and cultures were negative. The other four reported relief from symptoms but cultures remained positive. Seven of eight patients with toe onychomycosis reported symptom resolution with 100% TTO treatment, but cultures remained positive. A second case series reported satisfactory results in 18 of 23 cases following 100% TTO twice daily for fungal skin or nail infections.9
Adverse Effects
Adverse effects were reported infrequently; adverse effects are most commonly reported with use of 100% TTO products and include contact dermatitis with a vesicular rash and eczema with erythema, edema, and scaling.10-13 Ataxia and drowsiness occurred in two toddlers who ingested less than 15 ml of 100% TTO. Both children fully recovered following administration of activated charcoal and symptomatic support.14,15
Interactions
There are no reported interactions for TTO.
Contraindications
There are no contraindications to use of TTO products other than allergy. Pregnant or lactating woman should avoid use, as no safety information exists; the extent of cutaneous absorption has not been quantified.
Formulation and Dosage
TTO is available as an essential oil or as an ingredient in lotions, creams, or shampoos. Based on in vitro data, concentration should be 5-10% or higher.3-5 Twice daily topical application is the most common regimen used in trials. The Australian government has set a standard for Melaleuca alternifolia oil of at least 30% terpinen-4-ol and no more than 15% 1,8-cineole (eucalyptol).11 Other species such as M. quinquenervia and M. cajuputi produce niaouli oil and oil of cajuput, respectively, and are occasionally labeled as TTO. These oils have a very different composition, are used for aromatherapy, and should not be used as a substitute for M. alternifolia.2
Conclusion
In vitro studies have documented antimicrobial properties of TTO. (See Table 1 for a summary of clinical trials.) Two large controlled studies (Level of Evidence I and II) appear to demonstrate clinical effects for reduction of symptoms of tinea pedis and onychomycoses similar to topical pharmaceutical agents and there is further support from case series evidence. However, results of the controlled studies are severely weakened by major methodological limitations. TTO benefits have not been proven.
| Table 1-Human trials of tea tree oil (TTO) and cutaneous fungal infections | |||||||
| Trial | N | Fungal site | TTO | Control | Results | LOE | Limitations |
| Buck7 | 117 | nail | 100% oil | clotrimazole (C) | C = TTO | I | Major |
| Tong6 | 121 | skin | 10% cream | tolnaftate (T), placebo (P) | T = TTO > P | II | Major |
| Belaiche9 | 23 | nail and skin | 100% oil | NA | 18/23 reduced symptoms | V | Major |
| Walker8 | 12 | skin | 8% ointment | NA | 12/12 reduced symptoms, 8/12 negative cultures | V | Major |
| Walker8 | 8 | nail | 100% oil | NA | 7/8 reduced symptoms, 8/8 positive cultures | V | Major |
| = Level of Evidence | |||||||
Recommendation
Available evidence does not support a recommendation for tea tree oil use as a reliable topical antifungal therapy. Patients should be made aware that research has not yet confirmed TTO’s reliability or relative value compared to pharmaceutical agents. Based on the preliminary evidence, the adverse effects profile, and the relatively benign indications, TTO may be tried as a topical agent if desired by the patient. As 100% TTO is more likely to cause contact dermatitis, TTO-containing creams may be a wiser choice. Grade B
Dr. Harvey is a Clinical Pharmacy Specialist at drugstore.com in Seattle, WA.
References
1. Foster S, Tyler VE. Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Products. Binghamtom, NY: The Haworth Press; 1999.
2. The Review of Natural Products. St. Louis, MO: Facts and Comparisons; 2000.
3. Hammer KA, et al. In-vitro activity of essential oils, in particular Melaleuca alternifolia (tea tree) oil and tea tree oil products, against Candida spp. J Antimicrob Chemother 1998;42:591-595.
4. Nenoff P, et al. Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro. Skin Pharmacol 1996;9:388-394.
5. Concha M, et al. Antifungal activity of Melaleuca alternifolia (tea-tree) oil against various pathogenic organisms. J Am Podiatr Med Assoc 1998;88:489-492.
6. Tong MM, et al. Tea tree oil in the treatment of tinea pedis. Australas J Dermatol 1992;33:145-149.
7. Buck D, et al. Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. J Fam Pract 1994;38:601-605.
8. Walker M. Clinical investigation of Australian Melaleuca alternifolia oil for a variety of common foot problems. J Current Podiatry [Australian]. April, 1972.
9. Belaiche P. Treatment of skin infections with the essential oil of Melaleuca alternifolia. Phytotherapy 1985;15:15-17.
10. Apted JH. Contact dermatitis associated with the use of tea tree oil. Australas J Dermatol 1991;32:177.
11. Knight TE, Hausen BM. Melaleuca oil (tea tree oil) dermatitis. J Am Acad Dermatol 1994;30:423-427.
12. Selvaag E. Contact allergy due to tea tree oil and cross-sensitization to colophony. Contact Dermatitis 1994;31:124-125.
13. Bushan M, Beck MH. Allergic contact dermatitis from tea tree oil in a wart paint. Contact Dermatitis 1997;36:117-118.
14. Del Beccaro MA. Melaleuca oil poisoning in a 17-month-old. Vet Hum Toxicol 1995;37:557-558.
15. Jacobs MR, Hornfeldt CS. Melaleuca oil poisoning. J Toxicol Clin Toxicol 1994;32:461-464.
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