Over-the-counter and Natural Remedies for Onychomycosis: Do They Really Work?
Onychomycosis is a fungal infection of the nail unit that may lead to dystrophy and disfigurement over time. It accounts for up to 50% of all nail conditions, with toenails affected more commonly than fingernails. Onychomycosis may affect quality of life and increase the prevalence and severity of foot ulcers in patients with diabetes. Available oral agents approved by the US Food and Drug Administration (FDA) for the treatment of onychomycosis include terbinafine and itraconazole, which have demonstrated good efficacy but are associated with the risk of systemic side effects and drug-drug interactions. Topical medications that are FDA approved for onychomycosis include ciclopirox, efinaconazole, and tavaborole. These therapies generally have incomplete efficacy compared to systemic agents as well as long treatment courses and possible local side effects such as erythema and/or blisters. Given the need for safe, effective, and cost-effective options for onychomycosis therapy, there has been a renewed interest in natural and over-the-counter (OTC) alternatives. This review will synthesize the laboratory data, known antifungal mechanisms, and clinical studies assessing the efficacy of OTC and natural products for onychomycosis treatment.
Practice Points
- Natural remedies, including tea tree oil, natural topical cough suppressants, natural coniferous resin lacquer, Ageratina pichinchensis extract, and ozonized sunflower oil, have shown antifungal activities in in vitro studies.
- Some of these products have efficacy and appear to be safe in clinical studies.
- Larger randomized clinical trials demonstrating efficacy are required before we can recommend these products to our patients.
Comment
Due to the poor efficacy, long-term treatment courses, inability to use nail polish, and high cost associated with many FDA-approved topical treatments, along with the systemic side effects, potential for drug-drug interactions, and cost associated with many oral therapies approved for onychomycosis, there has been a renewed interest in natural remedies and OTC treatments. Overall, TTO, TCS, NCR, AP extract, and ozonized sunflower oil have shown efficacy in vitro against some dermatophytes, nondermatophytes, and molds responsible for onychomycosis. One or more clinical trials were performed with each of these agents for the treatment of onychomycosis. They were mostly small pilot studies, and due to differences in trial design, the results cannot be compared with each other or with currently FDA-approved treatments. We can conclude that because adverse events were rare with all of these therapies—most commonly skin irritation or mild skin pain—they exhibit good safety.
For TTO, there was no statistical difference between the clotrimazole and TTO treatment groups in mycologic cure, clinical assessment, or patient subjective assessment of the nails.29 Although there was an 80% complete cure in the butenafine and TTO group, it was 0% in the TTO group at week 36.30 Trial design, longer treatment periods, incorporation into nanocapsules, or combination treatment with other antifungal agents may influence our future use of TTO for onychomycosis, but based on the present data we cannot recommend this treatment in clinical practice.
With TCS, 27.8% of participants had a mycologic cure and 22.2% had complete clinical cure.40 Although it is difficult to draw firm conclusions from this small pilot study, there may be some benefit to treating toenail onychomycosis due to T mentagrophytes or C parapsilosis with TCS but no benefit in treating onychomycosis due to T rubrum, the more common cause of onychomycosis. Limitations of this study were lack of a placebo group, small sample size, wide variety of represented pathogens that may not be representative of the true population, and lack of stratification by baseline severity or involvement of nail. A larger randomized controlled clinical trial would be necessary to confirm the results of this small study and make formal recommendations.
In one clinical trial with NCR, mycologic cure was 65% at the end of the study.49 No participants achieved clinical cure, but 6 participants showed some improvement in the appearance of the nail. Because this study was small (N=15), it is difficult to draw firm conclusions.49 In another study with NCR, mycologic cure rates with NCR, amorolfine, and terbinafine were 13%, 8%, and 56%, respectively. Based on these results, NCR has similar antifungal efficacy to amorolfine but was inferior to oral terbinafine.50 A larger randomized controlled clinical trial with more homogenous and less severely affected patients and longer treatment periods would be necessary to confirm the results of these small studies and make formal recommendations.
Because there were no significant differences in clinical effectiveness of mycologic cure rates between AP lacquer 10% and ciclopirox lacquer 8% in one clinical trial,58 AP does not seem to be more effective than at least one of the current FDA-approved topical treatments; however, because AP lacquer 16.8% was shown to be more effective than AP lacquer 12.6% in one onychomycosis clinical trial, using higher concentrations of AP may yield better results in future trials.53
One trial comparing ozonized sunflower oil to ketoconazole cream 2% showed 90.5% and 13.5% cure rates, respectively.65 Although there is good in vitro antifungal activity and a clinical trial showing efficacy using ozonized sunflower oil for the treatment of onychomycosis, confirmatory studies are necessary before we can recommend this OTC treatment to our patients. Specifically, we will get the most data from large randomized controlled trials with strict inclusion/exclusion and efficacy criteria.
Conclusion
Over-the-counter and natural remedies may be an emerging area of research in the treatment of onychomycosis. This review summarizes the laboratory data and clinical trials on several of these agents and, when available, compares their clinical and mycologic efficacy with FDA-approved therapies. Shortcomings of some of these studies include a small study population, lack of adequate controls, nonstandardized mycologic testing, and abbreviated posttreatment evaluation times. It may be concluded that these products have varying degrees of efficacy and appear to be safe in the studies cited; however, at present, we cannot recommend any of them to our patients until there are larger randomized clinical trials with appropriate controls demonstrating their efficacy.
