Tea Tree Oil
Background
Tea tree oil is a volatile oil whose medicinal use dates back to the early 20th century when the Bundjabung aborigines of North and New South Wales extracted TTO from the dried leaves of the Melaleuca alternifolia plant and used it to treat superficial wounds.19 Tea tree oil has been shown to be an effective treatment of tinea pedis,20 and it is widely used in Australia as well as in Europe and North America.21 Tea tree oil also has been investigated as an antifungal agent for the treatment of onychomycosis, both in vitro22-28 and in clinical trials.29,30
In Vitro Data
Because TTO is composed of more than 100 active components,23 the antifungal activity of these individual components was investigated against 14 fungal isolates, including C albicans, T mentagrophytes, and Aspergillus species. The minimum inhibitory concentration (MIC) for α-pinene was less than 0.004% for T mentagrophytes and the components with the greatest MIC and minimum fungicidal concentration for the fungi tested were terpinen-4-ol and α-terpineol, respectively.22 The antifungal activity of TTO also was tested using disk diffusion assay experiments with 58 clinical isolates of fungi including C albicans, T rubrum, T mentagrophytes, and Aspergillus niger.24 Tea tree oil was most effective at inhibiting T rubrum followed by T mentagrophytes,24 which are the 2 most common etiologies of onychomycosis.5 In another report, the authors determined the MIC of TTO utilizing 4 different experiments with T rubrum as the infecting organism. Because TTO inhibited the growth of T rubrum at all concentrations greater than 0.1%, they found that the MIC was 0.1%.25 Given the lack of adequate nail penetration of most topical therapies, TTO in nanocapsules (TTO-NC), TTO nanoemulsions, and normal emulsions were tested in vitro for their ability to inhibit the growth of T rubrum inoculated into nail shavings. Colony growth decreased significantly within the first week of treatment, with TTO-NC showing maximum efficacy (P<.001). This study showed that TTO, particularly TTO-NC, was effective in inhibiting the growth of T rubrum in vitro and that using nanocapsule technology may increase nail penetration and bioavailability.31
Much of what we know about TTO’s antifungal mechanism of action comes from experiments involving C albicans. To date, it has not been studied in T rubrum or T mentagrophytes, the 2 most common etiologies of onychomycosis.5 In C albicans, TTO causes altered permeability of plasma membranes,32 dose-dependent alteration of respiration,33 decreased glucose-induced acidification of media surrounding fungi,32 and reversible inhibition of germ tube formation.19,34
Clinical Trials
A randomized, double-blind, multicenter trial was performed on 117 patients with culture-proven DLSO who were randomized to receive TTO 100% or clotrimazole solution 1% applied twice daily to affected toenails for 6 months.29 Primary outcome measures were mycologic cure, clinical assessment, and patient subjective assessment (Table 1). There were no statistical differences between the 2 treatment groups. Erythema and irritation were the most common adverse reactions occurring in 7.8% (5/64) of the TTO group.29
Another study was a double-blind, placebo-controlled trial involving 60 patients with clinical and mycologic evidence of DLSO who were randomized to treatment with a cream containing butenafine hydrochloride 2% and TTO 5% (n=40) or a control cream containing only TTO (n=20), with active treatment for 8 weeks and final follow-up at 36 weeks.30 Patients were instructed to apply the cream 3 times daily under occlusion for 8 weeks and the nail was debrided between weeks 4 and 6 if feasible. If the nail could not be debrided after 8 weeks, it was considered resistant to treatment. At the end of the study, the complete cure rate was 80% in the active group compared to 0% in the placebo group (P<.0001), and the mean time to complete healing with progressive nail growth was 29 weeks. There were no adverse effects in the placebo group, but 4 patients in the active group had mild skin inflammation.30