of head lice
Test materials applied with
well-soaked cotton bud
compared to various other oils
and neem insect repellent
Positive control: N,N-Diethyl-
Negative control: KY-Jelly,
inert lubricant gel
Lice applied to treated area
after 2 mins
TTO repelled 55% of
head ice from treated
area, followed by
peppermint (34%) and
TTO was most effective
at preventing lice from
feeding (60%) followed
by lavender (40%),
peppermint (28%) and
Most repellents were
not effective at causing
lice to leave the
treated site or prevent
18 subjects with
years); 18 subjects
used 100% TTO.
10 subjects used
5% TTO and
25 μl topical application 3
and 5 days after nickel
Treatment 1: 100% TTO
(complying with ISO4730);
Control 1: 100% macadamia
Treatment 2: 5% TTO lotion
100% TTO significantly
reduced the flare area
and erythema index
when compared to the
nickel-only sites. The
other substances had
no significant effect.
Assessment report on Melaleuca alternifolia (Maiden and Betch) Cheel, M. linariifolia Smith, M. dissitiflora F. Mueller and/or other species of Melaleuca, aetheroleum
s of hand-
et al. 2005
Study 1: 3 arm
and 5% TTO in
Tween 80 vs.
Soft Soap (SS)
Study 2: 2 arm
vs. Soft Soap
Study 1: 13
Study 2: 14
European Hand washing
Method’ against E. coli:
5ml of SS (control) or
product poured into
cupped hands pre-
moistened with tap water,
and 6 steps of hand
performed. Enough water
to create lather and hand
wash continued for 60s.
Hands rinsed under tap
water for 15s from distal to
proximal with fingertips
Treatments: HSW(5% TTO);
AHSW (5% TTO, 10%
alcohol); 5% TTO;
0.001%(v/v) Tween 80 in
sterile distilled water;
Control: SS recommended by
EN1499 (linseed oil;
potassium hydroxide; ethanol,
sterile distilled water)
TTO meets ISO4730;
and AHSW were
active than SS
HSW appeared slightly
more active than SS
(control) but difference
not significant. 5% TTO
in Tween 80 was
active than HSW.
Khalil et al.
as own control.
(testing 100% TTO)
25 μl of TTO applied
topically with a pipette to
area after 10 and 20mins
Treatment: 100% TTO
Control: no treatment
reduced the wheal and
Significant difference in
flare observed 30mins
injection and in wheal
observed 50 mins from
Koh et al.
testing 100% TTO
paraffin (5F/1M; 23-
25μl of TTO applied
area after 20mins
Treatment 1: 100% TTO
Treatment 2: liquid paraffin
Control: no treatment
Mean weal volume
after TTO application
(30mins and 60mins)
compared to control.
Liquid paraffin had no
significant effect on
weal or flare. No
difference in mean
flare area between
control and TTO.
TTO – Tea Tree Oil
F – Female
M – Male
Considerable research has been done on the metabolism of monoterpenes. After rapid dermal and/or
oral absorption, liver P450 mono-oxygenases are involved in biotransformation. Subsequently, 60-80%
of absorbed monoterpenes are excreted as glucuronides (Villar et al. 1994).
Cal and Krzyaniak (2006), Cal et al. (2006) and Cal (2008) studied the penetration behaviour of TTO
and pure constituents using a flow-through diffusion cells, human skin preparations and in vivo human
studies which represented infinitive dose and occlusive application conditions. TTO or pure terpene-4-ol
caused a significant increase in the skin accumulation of terpene-4-ol in the hydrophilic skin layers
(dermis and epidermis).
The process of terpene penetration into the skin and through the skin can be considered to be strongly
dependent on the experimental model used (choice of membrane, hydration level and dose) and on
the carrier for the penetrating terpene, while in vivo the effect of evaporation – shown to be 98%
needs to be considered.
Human pharmacokinetic data are not available for tea tree oil. In vitro dermal penetration studies
using human skin preparations indicate that dermal absorption of TTO components is relatively low, up
2-4% of applied dose and the main components observed to penetrate were terpene-4-ol and α-
terpineol. As the components of TTO are semi-volatile, the majority of the applied dose evaporates
from the surface of the skin (Cross et al. 2008).
Clinical trials have been performed to test the efficacy of topical TTO products for a range of conditions
including acne, wound healing, mycosis (oral candidiasis, denture stomatitis, onychomycosis, tinea and
tinea pedis), protozoan infections, herpes labialis, dandruff, tinea.
Assessment report on Melaleuca alternifolia (Maiden and Betch) Cheel, M. linariifolia Smith, M. dissitiflora F. Mueller
Bassett et al. 1990 and Enshaieh et al. 2007 conducted randomised controlled trials and reported on
the use of TTO for the treatment of mild to moderate acne.
A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne (Bassett et al.
A single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of
5% TTO gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide
lotion was performed. The results of this study showed that both 5% tea-tree oil and 5% benzoyl
peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed
and non-inflamed lesions (open and closed comedones), although the onset of action in the case of
tea-tree oil was slower. Fewer side effects were experienced by patients treated with tea-tree oil
(Bassett et al. 1990).
The efficacy of 5% topical TTO gel in mild to moderate acne vulgaris: A randomised, double-blind
placebo-controlled study (Enshaieh et al. 2007).
One study has been conducted on the possible efficacy of TTO in treatment of the acne vulgaris. It was
a randomised double-blind clinical trial performed in 60 patients with mild to moderate acne vulgaris.
They were randomly divided into two groups and were treated with TTO gel 5% (n=30) or placebo
(n=30). They were followed every 15 days for a period of 45 days. Response to treatment was
evaluated by the total acne lesions counting and acne severity index (ASI). The data was analysed
statistically using t-test and by SPSS program. There was a significant difference between TTO gel and
placebo in the improvement of the total acne lesions counting and also regarding improvement of the
ASI. In terms of total acne lesions counting and ASI, TTO gel was 3.55 times and 5.75 times more
effective than placebo respectively. Side-effects with both groups were relatively similar and tolerable.
The authors concluded that topical 5% TTO is an effective treatment for mild to moderate acne
vulgaris (Enshaieh et al. 2007).
Assessor’s Comment: 5% TTO gel showed to ameliorate acne lesions in two studies.
Feinblatt 1960 reported on the use of TTO for the treatment of furunculosis (boils). 35 patients (26
males and 9 females) with furuncles located in various sites (18 in the neck, 8 on the back, 6 in the
axilla areas, 1 on the scalp, 4 on the face and forehead, 4 on the forearm, 1 on the calf and 1 on the
external ear) many of them at multiple sites were enrolled in the study. Ten patients were given
expectant treatment and 25 were treated with TTO painting the surface over the furuncle freely with
the oil two or three times daily, after thoroughly cleaning the site. Results showed that, of the 10
untreated controls, five of the boils were finally incised and in five cases the infected site of the
furuncle was still apparent after eight days. In the 25 cases treated with TTO, only one boil required
Assessment report on Melaleuca alternifolia (Maiden and Betch) Cheel, M. linariifolia Smith, M. dissitiflora F. Mueller
incision and in 15 cases the infected site of the furuncle was removed completely in eight days. In six
cases the infected site of the furuncle, while still present after eight days, was reduced more than one-
half and in three cases the infected site was reduced less than half in eight days. As to local reactions,
three patients complained of slight temporary stinging.
In the same paper Feinblatt (1960) described a typical case report of a male patient aged 40 under
treatment for diabetes mellitus, who complained of recurrent boils. TTO was applied directly over a
large boil (3 x 3 cm), swollen, reddened and painful boil on his neck two or three times daily after
thorough cleansing. There was definite improvement within two days, most of the inflammation had
disappeared after four days and the skin healed after eight days with no untoward effects or local
reactions. The patient repeated the use of TTO whenever a new boil developed and every time the
further boils development aborted. The Author concluded that, due to its high germicidal activity
against Staphylococcus aureus and on the basis of rapid healing without scarring achieved in the
study, TTO may be used as an alternative option before surgical intervention in furunculosis.
Uncontrolled, open-label, pilot study of TTO solution in the decolonisation of MRSA positive wounds and
its influence on wound healing (Edmonson et al. 2011).
The primary aim of an uncontrolled case series study was to assess whether a TTO solution used in a
wound cleansing procedure could decolonise MRSA from acute and chronic wounds of mixed aetiology.
The secondary aim was to determine if the TTO solution influenced wound healing outcomes. The
product used was a water-miscible 10% v/v TTO solution. Nineteen participants with wounds
suspected of being colonised with MRSA were enrolled in a pilot study. Seven were subsequently
shown not to have MRSA and were withdrawn from the study. As many as 11 of the remaining 12
participants were treated with a wash solution of 3.3% TTO manually shaken in water; the solution
was applied as part of the wound cleansing regimen at each dressing change. Dressing changes were
three times per week or daily as deemed necessary by the study nurse following assessment. One
participant withdrew from the study before treatment. No participants were MRSA negative after
treatment. After treatment had been implemented, 8 out of the 11 treated wounds had begun to heal
and reduced in size as measured by computer planimetry. TTO did not appear to inhibit healing and
the majority of wounds reduced in size after treatment.
Two adverse events of pain were reported by participants who experienced pain during the cleansing
procedure that may or may not have been because of the irrigation with the TTO solution (Edmonson
A clinical investigation to determine the efficacy and safety of TTO use for vaginal douche and topical
application in the treatment of trichomonal vaginitis, C. albicans vaginitis and other vaginal infections
was performed. The medication studied was a special emulsified 40% solution of Australian TTO with
isopropropyl alcohol 13%. Hundred thirty cases of vaginal infections were investigated: trichomonal
vaginitis (n=96), C. albicans vaginitis (n=4), nulliparous cervicitis from Trichomonas vaginalis (n=20),
chronic endocervicitis (n=10). Australian TTO was found to be highly effective in treatment of
tricomonal vaginitis, C. albicans vaginitis, cervicitis and chronic endocervicitis (Peña 1962).
frequent cause of nail disease, ranging from 2% to 13%. Standard treatments include debridement,
topical medications, and systemic therapies.
Comparison of two topical preparations for the treatment of onychomycosis: TTO and clotrimazole
(Buck et al. 1994).
A double-blind, multicenter, randomised controlled trial was performed at two primary care health and
residency training centres and one private podiatrist's office to assess efficacy and tolerability of topical
application of 1% clotrimazole solution compared with that of 100% TTO for the treatment of toenail
The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients
received twice-daily application of either 1% clotrimazole solution (n=53) or 100% TTO oil (n=64) for
6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures
were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months
after the conclusion of therapy. Adverse reactions were erythema, irritation and oedema (7.8% in TTO
and 5.7% in clotrimazole group), which cause the dropping out of four (3%) of the initial participants.
The baseline characteristics of the treatment groups did not differ significantly. After 6 months of
therapy, the two treatment groups were comparable based on culture cure (clotrimazole = 11%, TTO
= 18%) and clinical assessment documenting partial or full resolution (clotrimazole = 61%, TTO =
60%). Three months later, about one half of each group reported continued improvement or resolution
(clotrimazole = 55%; TTO = 56%).
Topical therapy, including the two preparations presented in this paper, provide improvement in nail
appearance and symptomatology. The study shows that use of a topical preparation in conjunction
with debridement is an appropriate initial treatment strategy (Buck et al. 1994).
Assessor’s comment: the study shows efficacy of 100% TTO solution comparable to clotrimazole in the
treatment of onychomycosis.
Syed et al. 1999 conducted a double blind randomised controlled trial investigating the treatment of
onychomycosis. 40 patients were randomly allocated to the Treatment group of 2% butenafine
hydrochloride and 5% TTO and 20 patients were randomly allocated to the control group consisting of
a TTO cream of unspecified concentration. After 16 weeks of topical application three times daily and
covering with an occlusive plastic dressing, 80% in the treatment group were cured and no patients in
the control group were cured. TTO in the control cream did not show the expected response and TTO
was mixed with butenafine hydrochloride in the treatment group, it is difficult to determine whether
the TTO produced any effect in this group. Treatment in the control group was discontinued after 8
weeks so it is possible that the control treatment did not have sufficient time to render its full potency.
observed in the patients with HIV/AIDS.
Efficacy of melaleuca oral solution for the treatment of fluconazole refractory oral candidiasis in AIDS
patients (Jandourek et al. 1998, Vazquez & Zawawi 2002).
Efficacy of melaleuca oral solution, an USA branded non-prescription commercial mouthwash
A prospective, single centre, open-labelled study was performed on thirteen patients with AIDS and
oral candidiasis documented to be clinically refractory to fluconazole, as defined by failure to respond
to a minimum of 14 days of > or = 400 mg fluconazole per day. Additionally, patients had in in vitro
resistance to fluconazole, defined by minimal inhibitory concentrations of > or = 20 µg/ml.
Patients were given 15 ml Melaleuca oral solution four times daily to swish and expel for 2-4 weeks.
Resolution of clinical lesions of oral pseudomembranous candidiasis lesions evaluations were performed
weekly for 4 weeks and at the end of therapy for clinical signs of oral candidiasis. Quantitative yeast
cultures were performed at each evaluation.
A total of 13 patients were entered into the study, 12 were evaluable. At the 2-week evaluation, 7 out
of 12 patients had improved, none were cured, and 6 were unchanged. At the 4-week evaluation, 8 out
of 12 patients showed a response (2 cured, 6 improved), 4 were non-responders, and 1 had
deteriorated. A mycological response was seen in 7 out of 12 patients. A follow-up evaluation 2-4
weeks after therapy was discontinued revealed that there were no clinical relapses in the 2 patients
who were cured.
The authors concluded that melaleuca oral solution appeared to be effective as an alternative regimen
for AIDS patients with oropharyngeal candidiasis refractory to fluconazole (Jandourek et al. 1998).
The efficacy of alcohol-based and alcohol-free USA branded non-prescription commercial mouthwashes
containing TTO in patients with AIDS and fluconazole-refractory oropharyngeal candidiasis was
The prospective, single-centre, open-label study was performed in a university-based inner city
HIV/AIDS clinic. The study included 27 patients with AIDS and oral candidiasis clinically refractory to
fluconazole. Patients were randomised 1:1 to receive either alcohol-based or alcohol-free TTO
mouthwash four times daily for 2–4 weeks. Thirteen patients were enrolled into cohort called 1, and
treated with 15 ml of an alcohol-based TTO mouthwash 4 times daily for 2 weeks; 14 patients were
enrolled into cohort called 2 and treated with 5 ml of an alcohol-free TTO mouthwash 4 times daily for
2 weeks. The different amount of mouthwash used in the two groups was due to need to use an
equivalent quantity of TTO because the alcohol-based mouthwash was less concentrated than the non-
alcohol-based mouthwash. Additional 2 weeks of therapy were provided for patients who showed
clinical improvement but who had not demonstrated a complete clinical response at the end of the
initial 2 weeks. The main outcome measure was resolution of clinical lesions of oral candidiasis.
Evaluations were performed at 2 and 4 weeks for clinical signs and symptoms of oral candidiasis and
quantitative yeast cultures.
All C. albicans isolates showed some degree of in in vitro resistance to fluconazole. Overall, using a
modified intent-to-treat analysis, 60% of patients demonstrated a clinical response to the TTO
mouthwash (7 patients cured and 8 patients clinically improved) at the 4-week evaluation.
The authors concluded that both formulations of the TTO mouthwash appeared to be effective
alternative regimens for patients with AIDS suffering from oropharyngeal candidiasis refractory to
fluconazole (Vazquez & Zawawi 2002).
Assessor’s comment: These studies show a positive effect of TTO commercial preparations in patients
with AIDS affected by oropharyngeal candidiasis. No information on the concentration of TTO in the
preparations used in the studies is available. Moreover the studies were conducted on a small number
In vitro and in vivo activity of melaleuca alternifolia mixed with tissue conditioner on C. albicans
(Catalan et al. 2008).
Denture stomatitis is an inflammatory reaction of the palatal and alveolar mucosa underlying
removable dental prostheses. Denture stomatitis is more commonly seen in the maxillary mucosa than
in the mandibular mucosa.
A study was performed to identify in vitro and in vivo activity of TTO mixed with different tissue
conditioners on the C. albicans strain. Microbiological tests were used to isolate C. albicans from
patients with denture stomatitis. The in vitro antifungal activity of TTO against C. albicans was
determined when it was applied directly and when it was mixed with tissue conditioners (Fitt, Lynal,
Coe-Comfort). For the in vivo activity the responses of 27 denture stomatitis patients divided in three
arms (each of them with 9 patients) were evaluated over a period of 12 days: the control group
received Coe-Comfort tissue conditioner, treatment group 1 received 1 ml TTO mixed with 4 ml Coe-
Comfort and treatment 2 group received 2 ml Nystatin mixed with 3 ml Coe-Comfort.
In the in vitro study, Coe-Comfort or Fitt conditioners mixed with 1 ml, 20% (v/v) of TTO exhibited a
total inhibition of C. albicans. Patients treated with TTO mixed with Coe-Comfort showed a significant
decrease in palatal inflammation compared with those treated with Coe-Comfort (P = 0.001). In
addition, a significant inhibition of C. albicans growth was observed with TTO mixed with Coe-Comfort
compared with only Coe-Comfort (P = 0.000004). There was no difference between the treatment
arms at day 12. The data did however suggest the decrease in C. albicans was faster with Treatment 1
(TTO) than with Treatment 2 (Nystatin). Conclusions of authors were that TTO mixed with Coe-Comfort
tissue conditioner is effective in treating denture stomatitis (Catalan et al. 2008).
Assessor’s comment: This study has been conducted on a small number of patients, but suggests that
TTO can be useful as an adjuvant in the care of denture stomatitis.
Treatment of tinea pedis
Satchell et al. 2002a and Tong et al. 1992 conducted randomised controlled trials and reported on the
use of TTO for the treatment of tinea pedis.
Treatment of interdigital tinea pedis with 25% and 50% TTO solution: A randomised, placebo-
controlled, blinded study (Satchell et al. 2002a).
A randomised, controlled, double-blinded study to determine the efficacy and safety of 25% and 50%
TTO in the treatment of interdigital tinea pedis was conducted. One hundred and fifty-eight patients
with tinea pedis clinically and microscopy suggestive of a dermatophyte infection were randomised to
receive either placebo, 25% or 50% TTO mixed in ethanol and polyethylene glycol solution. Patients
applied the solution twice daily to affected areas for 4 weeks and were reviewed after 2 and 4 weeks of
treatment. There was a marked clinical response seen in 68% of the 50% TTO group and 72% of the
25% TTO group, compared to 39% in the placebo group. Mycological cure was assessed by culture of
skin scrapings taken at baseline and after 4 weeks of treatment. The mycological cure rate was 64% in
the 50% TTO group and 55% in the 25%
TTO group, compared to 31% in the placebo group. Four
severe dermatitis that improved quickly on stopping the study medication (Satchell et al. 2002a).
TTO in the treatment of tinea pedis (Tong et al. 1992).
One hundred and four patients completed a randomised, double-blind trial to evaluate the efficacy of
10% w/w TTO cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis.
Significantly more tolnaftate-treated patients (85%) than TTO (30%) and placebo-treated patients
(21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no
statistically significant difference between TTO and placebo groups. All three groups demonstrated
improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching
and burning. The TTO group (24/37) and the tolnaftate group (19/33) showed significant improvement
in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018
respectively). TTO cream (10% w/w) appears to reduce the symptomatology of tinea pedis as
effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure
(Tong et al. 1992).
Assessor’s comment: This RCT shows efficacy of cream containing 10% TTO in improving symptoms of
tinea pedis but without significant effects against the basic cause of pathology.
Treatment of vaginal infections of C. albicans with TTO (Belaiche 1985a).
A clinical study with TTO on 28 patients (average age 34), in full oestro-progestinic activity affected by
vaginitis caused by C. albicans was carried out. One vaginal capsule weighting 2 g and containing 0.2
grams of TTO was administered every night before sleeping for 90 days. Only one woman had felt
vaginal burning at the end of the first week and she stopped the treatment. 23 out of 27 patients
showed a complete cure with disappearance of burning and white discharge (leucorrhea). 4 of them
had to continue the treatment due to the persistence of leucorrhea. Biological examinations showed
the disappearance of C. albicans in 21 patients (Belaiche 1985a).
Treatment of skin infections with TTO (Belaiche 1985b).
A clinical study with TTO was conducted in 27 patients affected by different dermatological disorders
with the following results:
3 cases of intertrigo infected with C. albicans: application of pure TTO for 6 weeks - 2 months
of TTO was successful in 3 out of 4 patients.
2 cases of staphylococcal and streptococcal impetigo in children: twice a day application of TTO
a complete healing, acting on the infection and not on the sebaceous glands activity.
11 cases of nail infections by C. albicans: treatment with pure TTO twice a day for 3 months,
improvement in 3 patients.
1 case of pytiriasis versicolor [tinea versicolour caused by Malassezia and/or Trichophytum]:
Australian TTO: a natural antiseptic fungicidal agent (Shemesh & Mayo 1991)
A clinical trial with Australian TTO was undertaken for the treatment of various dermatological
disorders for six months in 50 patients. Several forms of TTO preparations were used: pure oil (100%),
lozenges with 1% TTO plus 2.5 mg ground leaf; and a 5% cream. 50 patients were supplied TTO for a
period of 1 to 4 weeks, depending on the severity of the condition being treated. All patients who
completed treatment were either cured, all showed remarkable improvement in their presenting
condition. One patient stopped the treatment after one day because of mild erythematous skin
sensitivity to the 100% TTO (Shemesh & Mayo 1991).
Recurrent herpes labialis
Use of deception to achieve double-blinding in a clinical trial of TTO for the treatment of recurrent
herpes labialis (Carson et al. 2008).
In a randomised, placebo-controlled trial of TTO for the treatment of recurrent herpes labialis (RHL), or
cold sores, deception was used to prevent volunteers from identifying their treatment allocation.
Volunteers received placebo (n=102) or TTO (n=112) ointment in preparation for their next episode of
RHL and were told, falsely, that the aroma of the ointments had been changed to prevent identification
of the treatment group. At the trial's end, of the volunteers who had used their ointment and
presented for treatment assessment (n=100), approximately 50% correctly guessed their treatment
allocation (P=0.774). Amongst volunteers that had not presented for treatment assessment (n=114),
12 volunteers did not provide blinding data and 46 did not open their tube. For the 56 volunteers who
opened their tube, less than half of those receiving TTO (44.4%) and only a small proportion of those
on placebo (17.2%) were able to correctly identify their treatment allocation. Among the volunteers
that were not treated, the P-value was 0.083. This study showed that the ethical use of deception may
provide effective blinding in challenging circumstances (Carson et al. 2008).
Antimicrobial activity of garlic, TTO, and chlorhexidine against oral microorganisms (Groppo et al.
Antimicrobial activities of TTO, garlic, and chlorhexidine solutions against oral microorganisms were
subjects used a control solution (second week), and were randomly divided into the three groups (third
week): G1- 0.12% chlorhexidine in a vehicle solution; G2 - 2.5% solution of a garlic (Allium sativum
L.) aqueous extract 1:1; and G3 - 0.2% TTO in vehicle solution and 0.5% Tween 80. Dishes containing
blood agar and Mitis Salivarius Bacitracin agar (MSB) were inoculated with the subjects' saliva
(collected twice a week). Total microorganisms and mutans streptococci were counted in blood agar
and MSB, respectively.
Chlorhexidine and garlic groups showed antimicrobial activity against mutans streptococci, but not
against other oral microorganisms. The TTO group showed antimicrobial activity against mutans
streptococci and other oral microorganisms. Maintenance of reduced levels of microorganisms was
observed only for garlic and TTO during the two consecutive weeks (fourth and fifth). Unpleasant taste
(chlorhexidine 40%, TTO 30%, garlic 100%), burning sensation (chlorhexidine 40%, TTO 60%, garlic
100%), bad breath (chlorhexidine 40%, TTO 20%, garlic 90%), and nausea (chlorhexidine 0%, TTO
10%, garlic 30%) were reported. The authors concluded that garlic and TTO might be an alternative to
chlorhexidine (Groppo et al. 2002).
Clinical and antibacterial effect of tea tree oil – a pilot study (Arweiler et al. 2000)
Arweiler et al. 2000 reported the results from a pilot, non-randomised study on the effect of TTO on
supragingival plaque formation and vitality. The study was performed with eight patients, which after
professional tooth cleaning were asked to refrain any mechanical cleaning and to rinse the mouth with
placebo (water) for 1 week, with chlorhexidine 0.1% (positive control) in a second and 0.34% TTO
water solution with milk as emulsifier in a third test week. Every test week was followed by a 10-day
washout in which normal tooth brushing with standard toothpaste was performed. The TTO reduced
neither the plaque index nor the plaque area relative to the placebo although there was a reduction in
the amount of vital bacteria compared to placebo. Chlorhexidine significantly reduced plaque area and
vital bacteria compared to placebo and reduced plaque index.
The effects of a tea tree oil-containing gel on plaque and chronic gingivitis (Soukoulis & Hirsch 2004)
The use of TTO for oral conditions such severe gingivitis was studied in a double-blind, longitudinal,
non-crossover trial with 49 medically fit non-smokers (24 males and 25 females) aged 18-60 years.
Subjects were randomly assigned to three groups and given either 2.5% TTO-gel, 0.2% chlorhexidine
gel, or a placebo gel to be applied with a toothbrush twice daily. Treatment effects were assessed
using the Gingival Index (GI), Papillary Bleeding Index (PBI) and plaque staining score at four and
eight weeks. The TTO group had significant reduction in PBI and GI scores. However, TTO did not
reduce plaque scores, which tended to increase over the latter weeks of the study period. The Authors
concluded that topical application of TTO gel to inflamed gingival tissue may be useful as an adjuvant
of chemotherapeutic periodontal therapy.
Minor skin lesions
A randomised, controlled trial of TTO topical preparations versus a standard topical regimen for the
clearance of MRSA colonisation (Dryden et al. 2004)
Two topical MRSA eradication regimes were compared in hospital patients: a standard treatment
included mupirocin 2% nasal ointment, chlorhexidine gluconate 4% soap, silver sulfadiazine 1% cream
versus a TTO regimen. The TTO regimen comprised TTO 10% cream applied to the anterior nostrils
three times a day for five days; TTO 5% body wash all over the body at least once a day for five days;
TTO 10% cream to skin lesions, wounds and ulcers, and also to axillae or groins as an alternative to
the body wash. One hundred and fourteen patients received standard treatment and 56 (49%) were
cleared of MRSA carriage. One hundred and ten received TTO regimen and 46 (41%) were cleared.
There was no significant difference between treatment regimens (Fisher’s exact test; P ¼ 0:0286).
Mupirocin was significantly more effective at clearing nasal carriage (78%) than TTO cream (47%; P ¼
0:0001), but TTO treatment was more effective than chlorhexidine or silver sulfadiazine at clearing
superficial skin sites and skin lesions. The TTO preparations were effective, safe and well tolerated and
could be considered in regimens for eradication of MRSA carriage (Dryden et al. 2004).
Assessor’s comment: this study shows the efficacy of a cream containing TTO 10% to clean skin
lesions, wounds and ulcers.
TTO as an alternative topical decolonisation agent for methicillin-resistant Staphylococcus aureus
(Caelli et al. 2000)
Clearance of MRSA was also investigated by Caelli et al. 2000 who conducted a pilot randomised
controlled trial on 30 hospital inpatients aged between 32 and 82 years. Fifteen patients were
randomised to the TTO treatment group consisting of 4% TTO nasal ointment and 5% TTO body wash.
Fifteen patients were randomised to the standard treatment group consisting of 2% mupirocin nasal
ointment and triclosan body wash. The TTO treatment combination appeared to perform better than
the standard treatment of mupirocin and triclosan although the difference was not statistically
Treatment of dandruff with 5% TTO shampoo (Satchell et al. 2002b).
The efficacy and tolerability of 5% TTO on mild to moderate dandruff vs. placebo was investigated in a
randomised, single-blind, parallel-group study. One hundred twenty-six male and female patients,
aged 14 years and older, were randomly assigned to receive either 5% TTO shampoo or placebo,
which was used daily for 4 weeks. The dandruff was scored on a quadrant-area-severity scale and by
patient self-assessment scores of scaliness, itchiness, and greasiness. The 5% TTO shampoo group
showed a 41% improvement in the quadrant-area-severity score compared with 11% in the placebo
group (P < 0.001). Statistically significant improvements were also observed in the total area of
involvement score, the total severity score, and the itchiness and greasiness components of the
patients’ self-assessments. The scaliness component of patient self-assessment improved but was not
statistically significant. There were no adverse effects. 5% TTO appears effective and well tolerated in
the treatment of dandruff (Satchell et al. 2002b).
Assessor’s comment: this study shows efficacy and good tolerability of a 5% TTO shampoo in the
treatment of dandruff.
Finally a case study describing a 5-day successful use of vaginal pessaries containing 200 mg of TTO in
vegetable basis for the treatment of vaginal discharge typical of anaerobic vaginosis was reported by
Clinical Treatment of Ocular Demodecosis by Lid Scrub With Tea Tree Oil (Gao et al. 2007)
Gao et al. 2007, following an in vitro observation that Demodex is resistant to a wide range of
antiseptic solutions but susceptible to TTO in a dose-dependant manner, reported on the results of a
retrospective review of an in vivo treatment with TTO of eleven patients with ocular Demodex. They
found that Demodex count dropped to zero for two consecutive visits in less than four weeks in eight
patients. Ten out of eleven patients showed different degrees of symptomatic relief and notable
reduction of inflammatory signs. A significant visual improvement was noted in six out of twenty-two
eyes which was associated with the development of a stable lipid tear film. The TTO lid scrub
effectively eradicated ocular Demodex and resulted in subjective and objective improvements, which
was interpreted a result in understanding , but caused notable irritation in 3 patients. Positive results
were interpreted as preliminary results useful in understanding Demodex pathogenicity in causing
several ocular surface diseases. Retrospective nature and the lack of using a standardized format to
grade symptoms as well as randomisation with lid scrub using baby shampoo and small number of
patients were recognised as a limitation of the value of this study (Gao et al. 2007).
Finally the results of a case study were described by Millar & Moore 2008 where 100% TTO was used
for the topical treatment of multiple warts, due to human papilloma virus, on the hand of a seven year
old girl. Salicylic acid (12%) and lactic acid (4%) was previously used on this condition but only
resulted in the temporary removal of the warts and they recurred in greater numbers. After five days
treatment with undiluted TTO, all warts were reduced in size. After a further 7 days, there was no
evidence of warts and complete reepithelialisation of the area. No recurrence has been reported.
A summary of these studies is presented in Table 4.