4. Natural Therapies
Given the challenges associated with available topical and systemic agents, there is a renewed interest in exploring alternative natural treatments for onychomycosis [19]. Natural onychomycosis therapies may have some important advantages over current treatments. They have the potential to be less expensive, particularly if classified as over-the-counter or complementary medications. Furthermore, they have shown low levels of adverse reactions in human trials (mostly skin irritation or mild pain) (Table 1), suggesting that these medications could be safer and more tolerable than standard therapies. Because of the complex nature and composition of bioactive constituents present in plant-based treatments, natural treatment modalities may carry a lower risk for the development of fungal resistance [23]. These qualities indicate potential for natural therapies to be employed as prophylactic agents against onychomycosis.
While a number of natural remedies have shown promising antifungal activity in vitro, clinical trials on these treatments are as yet in early stages. For example, essential oils like tea tree oil have demonstrated antifungal activity in vitro [24,25], but their efficacy has not been adequately confirmed against onychomycosis in human trials [26] (Table 1). Most human trials investigating natural therapies for onychomycosis have been small-scale pilot studies that are not directly comparable with trials on standard treatments due to differences in design and methodology.
A six-month clinical trial investigated Ageratina pichinchensis (AP), a plant used in traditional Mexican medicine, as a topical treatment for onychomycosis [27]. Results showed AP 10% lacquer to be equivalent to ciclopirox 8% lacquer in terms of effectiveness against onychomycosis [27], and a follow-up trial showed that higher concentrations of AP can improve patient outcomes [28]. Natural Coniferous Resin (NCR) lacquer showed a mycological cure rate of 65% in a preliminary observational study [29], but only 13% in a randomised controlled trial. The clinical trial showed nine months of daily-applied NCR lacquer to be about as effective as weekly-applied amorolfine 5% lacquer, but less effective than three months of once-daily oral terbinafine (250 mg) [30].
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Recent pilot studies suggest potential for other natural compounds as therapeutic options for onychomycosis. For example, propolis, an adhesive resinous compound produced by honeybees to seal and protect their hives from pathogenic agents, exhibits significant antifungal and anti-biofilm activities in vitro [31]. A pilot study assessing treatment of onychomycosis with topical ethanol propolis extract for six months showed complete mycological and clinical cure in 56.3% (n = 16), with no adverse events reported [31]. The over-the-counter topical cough suppressant Vicks VapoRub® also showed some effectiveness against onychomycosis in a small-scale uncontrolled pilot study (n = 18; mycological cure rate 27.8%; partial/complete clinical cure rate 55.6%/27.8%) [32]. This product contains a combination of active and inactive ingredients, including camphor, eucalyptus oil, menthol and thymol, that have shown in-vitro activity against dermatophytes. It has been suggested that Vicks VapoRub® may be a suitable onychomycosis treatment for people living with HIV due to its low cost, minimal side effects and compatibility with antiretroviral medications [33].
Further large well-designed randomised controlled trials are necessary to determine the efficacy of natural treatments and make formal recommendations as to their use in onychomycosis.
