Clinical Investigations – Research Article

Skin Appendage Disord 2020;6:14–18 Received: July 31, 2019

Accepted: September 10, 2019
DOI: 10.1159/000503305 Published online: October 25, 2019

An Open Study to Evaluate Effectiveness and

Tolerability of a Nail Oil Composed of Vitamin
E and Essential Oils in Mild to Moderate Distal
Subungual Onychomycosis
Aurora Alessandrini Michela Starace Francesca Bruni Bianca Maria Piraccini
Department of Experimental, Diagnostic and Specialty Medicine, Division of Dermatology, University of Bologna,
Bologna, Italy

Keywords after 6 months of follow-up (T3). Results: At the end of the

Onychomycosis · Topical therapy · Tocopherol acetate · Tea 12-month study, the majority of patients achieved a com-
tree oil · Oregano oil · Lime oil plete cure of onychomycosis (78.5%). All patients were very
satisfied by the treatment. No side effects were recorded.
Conclusions: The results of our study indicate that this new
Abstract topical antifungal containing vitamin E and essential oils of
Background: Onychomycosis is the most common nail dis- lime, oregano, and tea tree is an effective and safe option for
ease and can affect both fingernails and toenails. When pos- topical therapy of onychomycosis. This topical antifungal
sible, topical treatment is generally preferred both by pa- nail oil restructures the nail appearance, improving patient’s
tients and physicians because it is associated with lower risk adherence to therapy and reducing the risk of relapses,
of systemic side effects and drug interactions than oral anti- maintaining results over time. © 2019 The Author(s)
fungals, avoiding laboratory monitoring. Objective: The aim Published by S. Karger AG, Basel

of our study was to evaluate the efficacy, tolerability, and

patient’s compliance of a new topical antifungal containing
vitamin E and essential oils of lime, oregano, and tea tree. Introduction
Patients and Methods: We enrolled 20 patients with mild-
moderate distal subungual onychomycosis due to dermato- Onychomycosis is the most common nail infective
phytes or non-dermatophyte molds. The product was ap- disorder and it is responsible for about 50% of all consul-
plied once daily on the periungual tissues and on the nail tations for nail disorders. Onychomycosis has been re-
plate for 6 months. Follow-up without therapy continued for ported as a gender- and age-related disease, as it is more
another 6 months in order to evaluate the product’s effect prevalent in males and its prevalence increases with age
maintenance. Periodic evaluation of treatment efficacy was in both genders [1]. Predisposing factors include mainly
performed by standardized photography and mycological systemic diseases, i.e., diabetes mellitus, peripheral arte-
examination (KOH + culture) of the target nail at baseline rial disease, immunosuppression.
(T0), after 3 months (T1) and 6 months (T2) of therapy, and

© 2019 The Author(s) Aurora Alessandrini

Published by S. Karger AG, Basel Department of Experimental, Diagnostic and Specialty Medicine
Division of Dermatology, University of Bologna
E-Mail [email protected] This article is licensed under the Creative Commons Attribution-
NonCommercial-NoDerivatives 4.0 International License (CC BY- Via Massarenti, 1, IT–40138 Bologna (Italy)
www.karger.com/sad E-Mail aurora.alessandrini3 @ unibo.it
NC-ND) (http://www.karger.com/Services/OpenAccessLicense).
Usage and distribution for commercial purposes as well as any dis-
tribution of modified material requires written permission.
 In most of the cases, onychomycosis is caused by an- barrier to the permeation and diffusion of drugs, requir-
thropophylic dermatophytes of the Trichophyton species. ing the right vehicle and a long duration of therapy, usu-
Particularly, Trichophyton rubrum is the most common ally 6–8 months or longer, ideally until a healthy nail has
cause, followed by Trichophyton interdigitale. Scopulari- regrown [6]. The goal of onychomycosis therapy is both
opsis brevicaulis, Fusarium spp., and Aspergillus spp. are to eliminate the infecting fungal organism and to restore
the most common non-dermatophyte molds isolated in the normal appearance of the nail (mycological and clin-
onychomycosis, usually in the toenails. Other molds that ical cure, respectively). However, we must not forget that
have been isolated include Acremonium spp., Alternaria clinical cure does not always follow mycological cure, be-
spp., Scytalidium spp., and other less frequent species. cause toenails often show traumatic alterations or dystro-
Yeasts represent the last common cause of nail fungal in- phies that are not reversed by antifungal therapy.
fection, and Candida albicans and Candida parapsilosis The aim of our study was to evaluate the efficacy and
are the two most common isolates. Candida onychomy- tolerability of a new topical antifungal containing vitamin
cosis is seen in the hands of immunodepressed and dia- E and essential oil of lime, oregano, and tea tree. This
betic patients [2] and in patients under chronic steroid combination of essential oils, with low percentage vehic-
therapy. ulated in tocopheryl acetate, resulted in the most active
Onychomycosis can be associated with local pain, par- agents against dermatophytes and molds in in vitro tests.
esthesia, reduced quality of life, and impaired social inter-
actions and daily activities [3]. Both the toenails and fin-
gernails can be affected, with the toenails being more Materials and Methods
commonly involved, and it is commonly associated with
We enrolled 20 patients (13 males and 7 females, mean age: 45
a history of tinea pedis or hyperhidrosis [4]. Clinically,
years) with mild-moderate onychomycosis due to both dermato-
there are different clinical types of onychomycosis, de- phytes, T. rubrum (14/20) and T. interdigitalis (3/20), and nonder-
pending on the modality of nail invasion: distal subun- matophyte molds, Fusarium sp. (2/20) and Scopulariopsis bevicau-
gual onychomycosis (DSO), the most common type, lis (1/20). For all patients, the diagnosis was established through
white superficial onychomycosis, proximal subungual clinical examination, direct microscopy and/or culture examina-
tion. The viscous oily product, consisting of only 4 ingredients in
onychomycosis, or total onychomycosis.
a patented formulation, was applied once daily on the periungual
The clinical signs of DSO include white or yellow nail tissues and the nail plate for 6 months, but follow-up without ther-
discoloration, nail plate thickening with subungual hy- apy continued for another 6 months in order to evaluate the prod-
perkeratosis and onycholysis. The diagnosis of onycho- uct’s effect maintenance. Periodic evaluation of treatment efficacy
mycosis can be suspected on clinical features alone but was performed by standardized photography and mycology of the
target nail at baseline (T0), after 3 months (T1) and 6 months (T2)
laboratory isolation of the fungus through direct micros-
of therapy, and after 6 months of follow-up (T3). Treatment effi-
copy with potassium hydroxide (KOH) and culture ex- cacy and tolerability were also subjectively evaluated by patients,
amination still remains the gold standard. through a specific questionnaire exploring efficacy, tolerability,
Treatment is chosen depending on the modality of nail easiness of application, and pleasantness of the oil. None of the
invasion, fungus species, and the number of affected nails. patients was receiving any other systemic and/or topical treatment.
The difficulty in treating onychomycosis results from the
deep-seated nature of the infection within the nail unit
and the difficulty of drugs to effectively reach all sites. In Results
case of DSO involving more than 50% of the nail and
more than 3 nails, systemic oral therapy with terbinafine, Fourteen of the 20 enrolled patients concluded the
itraconazole, or fluconazole represents the first choice of study. Interestingly, among the 6 patients who dropped
treatment. On the contrary, if the nail invasion is restrict- out of the study, 4 stopped treatment before the scheduled
ed to less than 50% of the nail and less than 3 nails are time because they achieved a complete cure of the affect-
involved, the treatment is based on topical application of ed nail (2 patients at T1 and 2 patients at T2) and did not
antifungals, conveyed in cream, gel, or nail lacquers [2]. want to come to visit.
Topical therapy is generally preferred both by patients Patients were affected by mild-moderate onychomy-
and physicians because it is associated with lower risk of cosis due to T. rubrum (14/20), T. interdigitalis (3/20),
systemic side effects and drug interactions, avoiding labo- Fusarium sp. (2/20), and Scopulariopsis bevicaulis (1/20),
ratory monitoring [5]. However, the nail has a slow proved by mycology. After 3 months of therapy (T1), 17
growth rate and its composition makes it a formidable of the 20 enrolled patients were evaluated, because 2 of

Vitamin E and Essential Oils for Skin Appendage Disord 2020;6:14–18 15

Onychomycosis DOI: 10.1159/000503305
them reported a complete resolution and 1 dropped out Discussion
of the study for personal reasons. Of the examined pa-
tients, 3 patients were completely cured (17.6%) (Fig. 1), Onychomycosis is a very common fungal infection,
13 (76.4%) showed a considerable improvement, and 1 which needs a targeted treatment. Therapy requires sev-
remained stable (5.8%). eral months, as the nail grows very slowly, especially in
After 6 months of therapy (T2), 14 of the 17 patients the elderly. Drug choice relies on the type and severity of
examined in T1 came back to the follow-up visit (among onychomycosis and the associated comorbidities.
the 3 dropouts, 2 reported a complete resolution and 1 The most common type of onychomycosis is DSO and
dropped out for personal reasons). Seven of the 14 pa- lateral subungual onychomycosis, which is characterized
tients (50%) showed a complete cure of onychomycosis by a fungal invasion starting from the lateral or distal sites
(Fig. 2), while 6 patients showed a significant improve- of the nail plate. The affected nails usually show subun-
ment (42.8%) (Fig. 3) and 1 remained stable (7.1%). gual hyperkeratosis, onycholysis, and white or yellow dis-
Once the treatment was suspended, patients were coloration. DSO usually affects one or both of the great
asked to come back to the follow-up visit after 6 months toenails and is also usually associated with tinea pedis.
(T3) in order to evaluate long-term efficacy: 11 patients The choice of treatment for onychomycosis is often a
achieved a complete resolution (78.5%) (Fig 4), 2 patients challenge for the dermatologist and is influenced by sev-
showed an important improvement, and 1 remained sta- eral factors, such as the number of toes/fingers involved,
ble. Overall, 15 patients were cured by this new treatment, severity of the disease, and presence of associated system-
2 showed a significant improvement, 1 remained stable, ic diseases. Topical treatments are often the first choice in
and 2 patients dropped out. mild-moderate cases due to their lower risk of systemic
All patient found the treatment easy to apply with a side effects and drug interactions, but their effectiveness
pleasant texture and the product did not leave sticky res- is limited to the presence of hyperkeratosis, which inter-
idues or any sensation on the nails. No treatment-related feres with their absorption at the level of the nail plate.
side effects were recorded in any patient. All the 17 pa- Penetration of a topical antifungal through the nail plate
tients who were able to fill out the patients’ questionnaire requires a vehicle that is specifically formulated for trans­
were very satisfied by the treatment and would buy it if ungual delivery.
marketed. It is interesting to note that 11 patients stated The topical product utilized in this study for treating
to significantly improve after 3 months of therapy. mild to moderate DSO is very innovative in the formula-

Color version available online

Fig. 1. A patient affected by onychomycosis
completely cured after 3 months of thera-
py.
Color version available online

Fig. 2. A patient affected by onychomycosis completely cured after 6 months of therapy.

16 Skin Appendage Disord 2020;6:14–18 Alessandrini/Starace/Bruni/Piraccini

DOI: 10.1159/000503305
tion, thanks to a result of to the combination of natural tissue trophism. In nail diseases, oral tocopherol acetate
components. Vitamin E (tocopherol tocopheryl acetate) is one of the few effective treatments for yellow nail syn-
has a high antioxidant activity in its pure state and can drome due to its antioxidant effect and because it in-
accelerate cellular proliferation of fibroblasts and epithe- creases the speed of nail growth [8]. Recent studies
lial cells, favoring tissue growth [7]: for this reason, it has showed the high capacity of topical tocopherol tocoph-
been widely used in dermatology for years to improve eryl acetate in conveying pharmacological molecules in
tissues [9].
Tea tree oil is an essential oil obtained from Melaleuca
alternifolia leaves, which, incorporated into topical for-
mulations, has shown antibacterial, antifungal, and anti-

Color version available online

inflammatory properties [10, 11] with an exceptional skin
penetration [12]. Oregano essential oil from Origanum
vulgare leaves is able to inhibit the growth of various
pathogenic bacteria and fungi [13–16]. Lime essential oil
from Citrus aurantifolia peel has antimicrobial activity
against bacteria and fungi [13, 17, 18]. In West Africa,
lime is an essential ingredient in herbal medicine to treat
various infectious diseases, burns, and gonorrhea because
it is easily available and cheaper than the conventional
drugs. Lime mesocarp helps in prevention of pimples due
to its cleansing action on the skin [17].
The results obtained in our study indicate that this new
topical antifungal containing vitamin E and essential oil
of lime, oregano, and tea tree is an effective and safe op-
tion for topical therapy of onychomycosis and it can cer-
tainly represent one of the first choices of treatment in
these patients. In addition, this topical formulation is well
absorbed at the level of the nail plate, improving tropism
of the nail and the periungual tissues, and makes the nail
even more resistant to infections, thus reducing the risk
of relapses.
The clinical appearance of the nail already improves
from the first weeks of treatment, potentially contribut-
ing to a better compliance adherence in long-term thera-
py. In conclusion, our study showed that this new topical
antifungal is not only able to obtain excellent therapeutic
Fig. 3. A patient affected by onychomycosis with a significant im- results but is also capable of maintaining such results over
provement after 6 months of therapy. time.
Color version available online

Fig. 4. A patient affected by onychomycosis completely cured after 6 months of follow-up.

Vitamin E and Essential Oils for Skin Appendage Disord 2020;6:14–18 17

Onychomycosis DOI: 10.1159/000503305
 Statement of Ethics Disclosure Statement

Subjects have given their informed consent and the study pro- No conflicts of interest are declared.
tocol has been approved by the institute’s committee on human
research.
Funding Sources

None.

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DOI: 10.1159/000503305