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11.1 Introduction 316

11.2 Acaricidal activity 316

11.3 Anticarcinogenic 317

11.4 Antimicrobial 317

11.4.1 Antibacterial 317

11.4.1.1 Methicillin-Resistant Staphylococcus aureus 318

11.4.2 Antifungal 318

11.4.3 Antiviral 319

11.4.4 Microbes of the Oral Cavity 320

11.4.4.1 Activity of Listerine against Plaque and/or Gingivitis 321

11.4.4.2 Antiviral Listerine 321

11.4.4.3 Activity of Essential Oils 321

11.4.5 Controlling Microflora in Atopic Dermatitis 323

11.4.6 Odor Management for Fungating Wounds 323

11.5 Dissolution of Hepatic and Renal Stones 323

11.5.1 Gall and Biliary Tract Stones 323

11.5.2 Renal Stones 325

11.6 Functional Dyspepsia 325

11.7 Gastroesophageal reflux 326

11.8 Hyperlipoproteinemia 326

11.9 Irritable Bowel Syndrome 327

11.10 Medical Examinations 328

11.11 Nausea 329

11.12 Pain Relief 329

11.12.1 Dysmenorrhea 330

11.12.2 Headache 330

11.12.3 Infantile Colic 331

11.12.4 Joint Physiotherapy 331

11.12.5 Nipple Pain 331

11.12.6 Osteoarthritis 331

11.12.7 Postherpetic Neuralgia 331

11.12.8 Postoperative Pain 332

11.12.9 Prostatitis 332

11.12.10 Pruritis 332

11.13 Pediculicidal Activity 332

11.14 Recurrent Aphthous Stomatitis 333

11.15 Respiratory Tract 333

11.15.1 Menthol 333

11.15.1.1 Antitussive 334

11.15.1.2 Nasal Decongestant 334

11.15.1.3 Inhibition of Respiratory Drive and Respiratory Comfort 335

11.15.1.4 Bronchodilation and Airway Hyperresponsiveness 335

11.15.1.5 Summary 336

11.15.2 1,8-Cineole 336

11.15.2.1 Antimicrobial 336

11.15.2.2 Antitussive 337

11.15.2.3 Bronchodilation 337

11.15.2.4 Mucolytic and Mucociliary Effects 337

11.15.2.5 Anti-Inflammatory Activity 338

11.15.2.6 Pulmonary Function 339

11.15.2.7 Summary 341

11.15.3 Treatment with Blends Containing both Menthol and 1,8-Cineole 341

11.16 Allergic Rhinitis 342

11.17 Snoring 342

11.18 Swallowing Dysfunction 342

11.19 Conclusion 343

References 343

11.1 INTRODUCTION

For many, the term "aromatherapy" originally became associated with the concept of the holistic use of essential oils to promote health and well-being. As time has progressed and the psychophysiological effects of essential oils have been explored further, their uses to reduce anxiety and aid sedation have also become associated with the term. This is especially so since the therapy has moved into the field of nursing, where such activities are of obvious benefit to patients in a hospital environment. More importantly, the practice of aromatherapy (in English-speaking countries) is firmly linked to the inhalation of small doses of essential oils and their application to the skin in high dilution as part of an aromatherapy massage.

This chapter is concerned with the medical use of essential oils, given to the patient by all routes of administration to treat specific conditions and in comparably concentrated amounts. Studies that use essential oils in an aromatherapy-like manner, for example, to treat anxiety by essential oil massage, are therefore excluded here.

Of the literature published in peer-reviewed journals over the last 30 years, only a small percentage concerns the administration of essential oils or their components to humans in order to treat disease processes. These reports are listed below in alphabetical order of their activity. The exception is the section on the respiratory tract, where the many activities of the two principal components (menthol and 1,8-cineole) are discussed and related to respiratory pathologies.

All of the references cited are from peer-reviewed publications; a minority is open to debate regarding methodology and/or interpretation of results, but this is not the purpose of this compilation. Reports of individual case studies have been omitted.

11.2 ACARICIDAL ACTIVITY

A number of essential oils have been found to have effective acaricidal activity against infections in the animal world. Recent examples include Origanum onites against cattle ticks (Coskun et al.,

2008) and Cinnamomum zeylanicum against rabbit mange mites (Fichi et al., 2007). In comparison to veterinary research, there have been few investigations into human acaricidal infections.

The scabies mite, Sarcoptes scabiei var. hominis, is becoming increasingly resistant to existing acaricidal compounds such as lindane, benzyl benzoate, permethrin, and oral ivermectin. The potential use of a 5% Melaleuca alternifolia essential oil solution to treat scabies infections was investigated in vitro. It was found to be highly effective at reducing mite survival times and the main active component was terpinen-4-ol. However, the in vivo effectiveness was only tested on one individual, in combination with benzyl benzoate and ivermectin (Walton et al., 2004).

A double-blind, randomized, parallel group study was used to compare the effects of 25% w/w benzyl benzoate emulsion with 20% w/w Lippia multiflora essential oil emulsion in the treatment of scabies infection in 105 patients. Applied daily, the cure rates for the oil emulsion were 50%, 80%, and 80% for 3, 5, and 7 days, respectively, compared to 30%, 60%, and 70% for the benzyl benzoate emulsion. There were also less adverse reactions to the oil emulsion, leading it to be considered as an additional formulation for the treatment of scabies (Oladimeji et al., 2005).

Although not an infection, the lethal activity of essential oils toward the house dust mite (Dermatophagoides farina and Dermatophagoidespteronyssinus) is important as these mites are a major cause of respiratory allergies and an etiologic agent in the sensitization and triggering of asthma in children. Numerous studies have been conducted, including the successful inclusion of Eucalyptus globulus in blanket washing solutions (Tovey and McDonald, 1997), the high acaricidal activity of clove, rosemary, eucalyptus, and caraway (El-Zemity et al., 2006), and of tea tree and lavender (Williamson et al., 2007).

11.3 ANTICARCINOGENIC

Despite the popularity of in vitro experimentation concerning the cellular mechanisms of carcinogenic prevention by essential oil components (mainly by inducing apoptosis), there is no evidence that the direct administration of essential oils can cure cancer. There is evidence to suggest that the mevalonate pathway of cancer cells is sensitive to the inhibitory actions of dietary plant isoprenoids (e.g., Elson and Yu, 1994; Duncan et al., 2005). Animal testing has shown that some components can cause a significant reduction in the incidence of chemically induced cancers when administered before and during induction (e.g., Reddy et al., 1997; Uedo et al., 1999).

Phase II clinical trials have all involved perillyl alcohol. Results demonstrated that despite preclinical evidence, there appeared to be no anticarcinogenic activity in cases of advanced ovarian cancer (Bailey et al., 2002), metastatic colorectal cancer (Meadows et al., 2002), and metastatic breast cancer (Bailey et al., 2008). Only one trial has demonstrated antitumor activity as evidenced by a reduction of tumor size in patients with recurrent malignant gliomas (Orlando da Fonseca et al., 2008).

11.4 ANTIMICROBIAL

Considering that the majority of essential oil research is directed toward antimicrobial activity, there is a surprising lack of corresponding in vivo human trials. This is disappointing since the topical and systemic application of essential oils to treat infection is a widespread practice among therapists with (apparently) good results.

11.4.1 Antibacterial

Antibiotics that affect Propionibacterium acnes are a standard treatment for acne but antibiotic resistance is becoming prevalent. A preliminary study of 126 patients showed that topical 2% essential oil of Ocimum gratissimum (thymol chemotype) in a hydrophilic cream base was more effective than 10% benzyl peroxide lotion at reducing the number of lesions when applied twice daily for 4 weeks (Orafidiya et al., 2002).

In a randomized, single-blind, parallel-group-controlled trial, the same group examined the effects of the addition of aloe vera gel at varying concentrations to the Ocimum gratissimum cream and compared its activity with 1% clindamycin phosphate. In the 84 patients with significant acne, it was found that increasing the aloe gel content improved efficacy; the essential oil preparations formulated with undiluted or 50% aloe gels were more effective at reducing lesions than the reference product. The aloe vera gels alone had minimal activity (Orafidiya et al., 2004).

A later report judged the efficacy of a 5% Melaleuca alternifolia gel in the amelioration of mild to moderate acne, since a previous study (Raman et al., 1995) had demonstrated the effectiveness of tea tree oil components against Propionibacterium acnes. The randomized, double-blind, placebo-controlled trial used 60 patients who were given the tea tree oil gel or the gel alone twice daily for 45 days. The total acne lesion count was significantly reduced by 43.64% and the acne severity index was significantly reduced by 40.49% after the tea tree oil treatment, as compared to the placebo scores of 12.03% and 7.04%, respectively (Enshaieh et al., 2007).

11.4.1.1 Methicillin-Resistant Staphylococcus aureus

A number of papers have demonstrated the in vitro effects of various essential oils against methicillin-resistant Staphylococcus aureus (MRSA); for example, Lippia origanoides (Dos Santos et al., 2004), Backhousia citriodora (Hayes and Markovic, 2002), Mentha piperita, Mentha arvensis, and Mentha spicata (Imai et al., 2001), and Melaleuca alternifolia (Carson et al., 1995). There have been no trials involving the use of essential oils to combat active MRSA infections, although there have been two studies involving the use of tea tree oil as a topical decolonization agent for MRSA carriers.

A pilot study compared the use of 2% mupirocin nasal ointment and triclosan body wash (routine care) with 4% Melaleuca alternifolia essential oil nasal ointment and 5% tea tree oil body wash in 30 MRSA patients. The interventions lasted for a minimum of 3 days and screening for MRSA was undertaken at 48 and 96 h post-treatment from sites previously colonized by the bacteria. There was no correlation between length of treatment and outcome in either group. Of the tea tree oil group, 33% were initially cleared of MRSA carriage while 20% remained chronically infected at the end of the treatment; this was in comparison with routine care group of 13% and 53%, respectively. The trial was too small to provide significant results (Caelli et al., 2000).

A randomized, controlled trial compared the use of a standard regime for MRSA decolonization with Melaleuca alternifolia essential oil. The 5-day study involved 236 patients. The standard treatment group was given 2% mupirocin nasal ointment thrice daily, 4% chlorhexidine gluconate soap as a body wash once daily, and 1% silver sulfadiazine cream for skin lesions, wounds, and leg ulcers once daily. The tea tree oil group received 10% essential oil cream thrice daily to the nostrils and to specific skin sites and 5% essential oil body wash at least once daily. In the tea tree oil group, 41% were cleared of MRSA as compared to 49% using the standard regime; this was not a significant difference. Tea tree oil cream was significantly less effective at clearing nasal carriage than mupi-rocin (47% compared to 78%), but was more effective at clearing superficial sites than chlorhexidine or silver sulfadiazine (Dryden et al., 2004).

11.4.2 Antifungal

The essential oil of Citrus aurantium var. amara was used to treat 60 patients with tinea corporis, cruris, or pedis. One group received a 25% bitter orange (BO) oil emulsion thrice daily, a second group was treated with 20% bitter orange oil in alcohol (BOa) thrice daily, and a third group used undiluted BO oil once daily. The trial lasted for 4 weeks and clinical and mycological examinations were performed every week until cure, which was defined as an elimination of signs and symptoms. In the BO group, 80% of patients were cured in 1-2 weeks and the rest within 2-3 weeks. By using BOa, 50% of patients were cured in 1-2 weeks, 30% in 2-3 weeks, and 20% in 3-4 weeks. With the undiluted essential oil, 25% of patients did not continue treatment, 33.3% were cured in 1 week, 60% in 1-2 weeks, and 6.7% in 2-3 weeks (Ramadan et al., 1996).

A double-blind, randomized, placebo-controlled trial investigated the efficacy of 2% buten-afine hydrochloride cream with added 5% Melaleuca alternifolia essential oil in 60 patients with toenail onychomycosis. After 16 weeks, 80% of patients in the treatment group were cured, as opposed to none in the control group (Syed et al., 1999). However, butenafine hydrochloride is a potent antimycotic in itself and the results were not compared with this product when used alone.

After an initial in vitro study, which showed that the essential oil of Eucalyptuspauciflora had a strong fungicidal activity against Epidermophyton floccosum, Microsporum canis, Microsporum nanum, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton tonsurans, and Trichophyton violaceum, an in vivo trial was commenced. Fifty patients with confirmed dermatophytosis were treated with 1% v/v essential oil twice daily for 3 weeks. At the end of the treatment, a cure was demonstrated in 60% of patients with the remaining 40% showing significant improvement (Shahi et al., 2000).

On the surmise that infection with Pityrosporum ovale is a major contributing factor to dandruff and that anti-Pityrosporum drugs such as nystatin were proven effective treatments, the use of 5% Melaleuca alternifolia essential oil was investigated. In this randomized, single-blind, parallel-group study tea tree oil shampoo or placebo shampoo was used daily for 4 weeks by 126 patients with mild to moderate dandruff. In the treatment group, the dandruff severity score showed an improvement of 41%, as compared to 11% in the placebo group. The area involvement and total severity scores also demonstrated a statistically significant improvement, as did itchiness and greasiness. Scaliness was not greatly affected. The condition resolved for one patient in each group and so ongoing application of tea tree oil shampoo was recommended for dandruff control (Satchell et al., 2002a).

For inclusion in a randomized, double-blind, controlled trial, 158 patients with the clinical features of intertriginous tinea pedis and confirmed dermatophyte infection were recruited. They were administered 25% or 50% Melaleuca alternifolia essential oil (in an ethanol and polyethylene glycol vehicle) or the vehicle alone, twice daily for 4 weeks. There was an improvement in the clinical severity score, falling by 68% and 66% in the 25% and 50% tea tree oil groups, in comparison with 41% for the placebo. There was an effective cure in the 25% and 50% tea tree oil and placebo groups of 48%, 50%, and 13%, respectively. The essential oil was less effective than standard topical treatments (Satchell et al., 2002b).

The anticandida properties of Zataria multiflora essential oil and its active components (thymol, carvacrol, and eugenol) were demonstrated in vitro by Mahmoudabadi et al. (2006). A randomized, clinical trial was conducted using 86 patients with acute vaginal candidiasis. They were treated with a cream containing 0.1% Zataria multiflora essential oil or 1% clotrimazole once daily for 7 days. Statistically significant decreases in vulvar pruritis (80.9%), vaginal pruritis (65.5%), vaginal burning (73.95), urinary burning (100%), and vaginal secretions (90%) were obtained by the essential oil treatment as compared to the clotrimazole treatment of 73.91%, 56.7%, 82.1%, 100%, and 70%, respectively. In addition, the Zataria multiflora cream reduced erythema and satellite vulvar lesions in 100% of patients, vaginal edema in 100%, vaginal edema in 83.3%, and vulvo-vaginal excoriation and fissures in 92%. The corresponding results for clotrimazole were 100%, 100%, 76%, and 88%. In terms of overall efficacy, the rates of improvement were 90% and 74.8% for the Zataria multiflora and clotrimazole groups, respectively. Use of the cream alone provided no significant changes (Khosravi et al., 2008).

11.4.3 Antiviral

The in vitro studies that have been conducted so far indicate that many essential oils possess antiviral properties, but they affect only enveloped viruses and only when they are in the free state, that is, before the virus is attached to, or has entered the host cell (e.g., Schnitzler et al., 2008). This is in contrast to the majority of synthetic antiviral agents, which either bar the complete penetration of viral particles into the host cell or interfere with viral replication once the virus is inside the cell.

A randomized, investigator-blinded, placebo-controlled trial used 6% Melaleuca alternifolia essential oil gel to treat recurrent herpes labialis. It was applied five times daily and continued until re-epithelialization occurred and the polymerase chain reaction (PCR) for Herpes simplex virus was negative for two consecutive days. The median time to re-epithelialization after treatment with tea tree oil was 9 days as compared to 12.5 days with the placebo, which is similar to reductions caused by other topical therapies. The median duration of PCR positivity was the same for both groups (6 days) although the viral titers appeared slightly lower in the oil group on days 3 and 4. None of the differences reached statistical significance, probably due to the small group size (Carson et al., 2001).

Children below 5 years were enrolled in a randomized trial to test a 10% v/v solution of the essential oil of Backhousia citriodora against molluscum contagiosum (caused by Molluscipox-virus). Of the 31 patients, 16 were assigned to the treatment group and the rest to the control of olive oil. The solutions were applied directly to the papules once daily at bedtime for 21 days or until the lesions had resolved. In the essential oil group, five children had a total resolution of lesions and four had reductions of greater than 90% at the end of 21 days. In contrast, none of the control group had any resolution or reduction of lesions by the end of the study period (Burke et al., 2004).

A study was conducted on 60 patients who were chronic carriers of hepatitis B or C. The essential oils of Cinnamomum camphora ct 1,8-cineole, Daucus carota, Ledum groelandicum, Laurus nobilis, Helichrysum italicum, Thymus vulgaris ct thujanol, and Melaleuca quinquenervia were used orally in various combinations. They were used as a monotherapy or as a complement to allopathic treatment. The objectives of treatment were normalization of transaminase levels, reduction of viral load, and stabilization or regression of fibrosis. There was an improvement of 100%, when patients with hepatitis C were given bitherapy with essential oils. With essential oil monotherapy, improvements were noted in 64% of patients with hepatitis C and there were two cures of hepatitis B (Giraud-Robert, 2005).

11.4.4 Microbes of the Oral Cavity

The activities of essential oils against disease-producing microbes in the oral cavity have been documented separately because there are numerous reports of relevance. The easy administration of essential oils in mouthrinses, gargles, and toothpastes, and the success of such commercial preparations, has no doubt led to the popularity of this research.

The in vitro activities of essential oils against the oral microflora are well documented and these include effects on cariogenic and periodontopathic bacteria. One example is the in vitro activity of Leptospermum scoparium, Melaleuca alternifolia, Eucalyptus radiata, Lavandula officinalis, and Rosmarinus officinalis against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Streptococcus mutans. The essential oils inhibited all of the test bacteria, acting bactericidally except for Lavandula officinalis. In addition, significant adhesion-inhibiting activity was shown against Streptococcus mutans by all essential oils and against Porphyromonas gingivalis by tea tree and manuka (Takarada et al., 2004).

There have been at least six in vivo studies concerning the activity of individual essential oils against the microflora of the oral cavity. In addition, a review of the literature finds a surprising number of in vivo papers that detail the activities of "an essential oil mouthrinse." Closer examination reveals that the essential oil mouthrinse is the commercial product, Listerine. Although Listerine contains 21% or 26% alcohol (depending on the exact product), a 6-month study has shown that it contributes nothing to the efficaciousness of the mouthrinse (Lamster et al., 1983). The active ingredients are 1,8-cineole (0.092%), menthol (0.042%), methyl salicylate (0.06%), and thymol (0.64%). For this reason, a small random selection of such papers is included below.

11.4.4.1 Activity of Listerine against Plaque and/or Gingivitis

An observer-blind, 4-day plaque regrowth, crossover study compared the use of Listerine® with a triclosan mouthrinse and two placebo controls in 32 volunteers. All normal hygiene procedures were suspended except for the rinses. The triclosan product produced a 45% reduction in plaque area and a 12% reduction in plaque index against its placebo, in comparison with 52% and 17%, respectively, for the essential oil rinse. The latter was thus deemed more effective (Moran et al., 1997).

A similar protocol was used to compare the effects of Listerine against an amine fluoride/stannous fluoride-containing mouthrinse (Meridol®) and a 0.1% chlorhexidine mouthrinse (Chlorhexamed®) in inhibiting the development of supragingival plaque. On day 5 of each treatment, the results from 23 volunteers were evaluated. In comparison with their placebos, the median plaque reductions were 12.2%, 23%, and 38.2% for the fluoride, essential oil, and chlorhexidine rinses, respectively. The latter two results were statistically significant (Riep et al., 1999).

After the assessment for the presence of gingivitis and target pathogens (Porphyromonas gingivalis, Fusobacterium nucleatum, and Veillonella sp.) and total anaerobes, 37 patients undertook a twice daily mouthrinse with Listerine for 14 days. After a washout period, the study was conducted again using a flavored hydroalcoholic placebo. The results of this randomized, doubleblind, crossover study showed that the essential oil rinse significantly lowered the number of all target pathogens by 66.3-79.2%, as compared to the control (Fine et al., 2007).

The effect of adding Listerine mouthrinse to a standard oral hygiene regime in 50 orthodontic patients was examined. The control group brushed and flossed twice daily, whereas the test group also used the mouthrinse twice daily. Measurements of bleeding, gingival, and plaque indices were conducted at 3 and 6 months. All three indices were significantly lowered in the test group as compared to the control at both time intervals (Tufekci et al., 2008).

The same fixed combination of essential oils that is found in Listerine mouthrinse has been incorporated into a dentifrice. Such a dentifrice was used in a 6-month double-blind study to determine its effect on the microbial composition of dental plaque as compared to an identical dentifrice without essential oils. Supragingival plaque and saliva samples were collected at baseline and their microbial content characterized, after which the study was conducted for 6 months. The essential oil dentifrice did not significantly alter the microbial flora and opportunistic pathogens did not emerge, nor was there any sign of developing resistance to the essential oils in tested bacterial species (Charles et al., 2000).

The same dentifrice was examined for antiplaque and antigingivitis properties in a blinded, randomized, controlled trial. Before treatment, 200 patients were assessed using a plaque index, a modified gingival index (GI), and a bleeding index. The dentifrice was used for 6 months, after which another assessment was made. It was found that the essential oil dentifrice had a statistically significant lower whole-mouth and interproximal plaque index (18.3% and 18.1%), mean GI (16.2% and 15.5%), and mean bleeding index (40.5% and 46.9%), as compared to the control. It was therefore proven to be an effective antiplaque and antigingivitis agent (Coelho et al., 2000).

11.4.4.2 Antiviral Listerine

A trial was conducted to examine whether a mouthrinse could decrease the risk of viral crosscon-tamination from oral fluids during dental procedures. Forty patients with a perioral outbreak of recurrent herpes labialis were given a 30-s mouthrinse with either water or Listerine. Salivary samples were taken at baseline, immediately following the rinse and 30 min after the rinse and evaluated for the viral titer. Infectious virions were reduced immediately to zero postrinse and there was a continued significant reduction 30 min postrinse. The reduction by the control was not significant (Meiller et al., 2005).

11.4.4.3 Activity of Essential Oils

The antibacterial activity of the essential oil of Lippia multiflora was first examined in vitro for antimicrobial activity against ATCC strains and clinical isolates of the buccal flora. A significant activity was found, with an MBC of 1/1400 for streptococci and staphylococci, 1/800 for enterobac-teria and neisseria, and 1/600 for candida. A mouthwash was prepared with the essential oil at a 1/500 dilution and this was used in two clinical trials.

The buccodental conditions of 26 French children were documented by measuring the percentage of dental surface free of plaque, gum inflammation, and the papillary bleeding index (PBI). After 7 days of rinsing with the mouthwash for 2 min, the test group was found to have a reduction of dental plaque in 69% of cases and a drop in PBI with a clear improvement of gum inflammation in all cases. The second trial was conducted in the Cote d'lvoire with 60 adult patients with a variety of conditions. After using the mouthwash after every meal for 5 days, it was found that candidiasis had disappeared in most cases, gingivitis was resolved in all patients, and 77% of dental abscesses had resorbed (Pelissier et al., 1994).

Fluconazole-refractory oropharyngeal candidiasis is a common condition in HIV patients. Twelve such patients were treated with 15 mL of a Melaleuca alternifolia oral solution (Breath-Away) four times daily for 2 weeks, in a single center, open-label clinical trial. The solution was swished in the mouth for 30-60 s and then expelled, with no rinsing for at least 30 min. Clinical assessment was carried out on days 7 and 14 and also on days 28 and 42 of the follow-up. Two patients were clinically cured and six were improved after the therapy; four remained unchanged and one deteriorated. The overall clinical response rate was thus 67% and was considered as a possible alternative anti-fungal treatment in such cases (Jandourek et al., 1998).

A clinical pilot study compared the effect of 0.34% Melaleuca alternifolia essential oil solution with 0.1% chlorhexidine on supragingival plaque formation and vitality. Eight subjects participated, with a 10-day washout period between each treatment regime of 1 week. The plaque area was calculated using a stain and plaque vitality was estimated using a fluorescence technique. Neither of these parameters was reduced by the tea tree oil treatment (Arweiler et al., 2000).

A gel containing 2.5% Melaleuca alternifolia essential oil was used in a double-blind, longitudinal noncrossover trial and compared with a chlorhexidine gel positive control and a placebo gel in the treatment of plaque and chronic gingivitis. The gels were applied as a dentifrice twice daily by 49 subjects for 8 weeks and the treatment was assessed using a gingival index (GI), a PBI, and a plaque staining score. The tea tree group showed a significant reduction in PBI and GI scores, although plaque scores were not reduced. It was apparent that the tea tree gel decreased the level of gingival inflammation more than the positive or negative controls (Soukoulis and Hirsch, 2004).

A mouthcare solution consisting of an essential oil mixture of Melaleuca alternifolia, Mentha piperita, and Citrus limon in a 2:1:2 ratio diluted in water to a 0.125% solution was used to treat oral malodor in 32 intensive care unit patients, 13 of whom were ventilated. The solution was used to clean the teeth, tongue, and oral cavity twice daily. The level of malodor was assessed by a nurse using a visual analogue scale, and volatile sulfur compounds (VSC) were measured via a probe in the mouth, before, 5 and 60 min after treatment. On the second day, the procedure was repeated using benzydamine hydrochloride (BH), which is normally used for oral hygiene, instead of essential oil solution. The perception of oral malodor was significantly lowered after the essential oil treatment but not after the BH treatment. There was a decrease in VSC levels at 60 min for both treatment groups, but not after 5 min for the oil mixture. The results suggested that just one session with the essential oil mixture could improve oral malodor and VSC in intensive care patients (Hur et al., 2007).

The essential oil of Lippia sidoides (rich in thymol and carvacrol) was used in a double-blind, randomized, parallel-armed study against gingival inflammation and bacterial plaque. Fifty-five patients used a 1% essential oil solution as a mouthrinse twice daily for 7 days and the results were compared with a positive control, 0.12% chlorhexidine. Clinical assessment demonstrated decreased plaque index and gingival bleeding scores as compared to the baseline, with no significant difference between test and control. The essential oil of Lippia sidoides was considered a safe and effective treatment (Botelho et al., 2007).

11.4.5 Controlling Microflora in Atopic Dermatitis

Rarely found on healthy skin, Staphylococcus aureus is usually present in dry skin and is one of the factors that can worsen atopic dermatitis. Toxins and enzymes deriving from this bacteria cause skin damage and form a biofilm from fibrin and glycocalyx, which aids adhesion to the skin and resistance to antibiotics. An initial in vitro study found that a mixture of xylitol (a sugar alcohol) and farnesol was an effective agent against Staphylococcus aureus; xylitol inhibited the formation of glycocalyx whereas farnesol dissolved fibrin and suppressed Staphylococcus aureus growth without affecting Staphylococcus epidermidis (Masako et al., 2005a).

The same mixture of xylitol and farnesol was used in a double-blind, randomized, placebo-controlled study of 17 patients with mild to moderate atopic dermatitis on their arms. A skin-care cream containing 0.02% farnesol and 5% xylitol or the cream alone was applied to either the left or the right arms for 7 days. The ratio of Staphylococcus aureus to other aerobic skin microflora was significantly decreased in the test group compared to placebo, from 74% to 41%, while the numbers of coagulase-negative staphylococci increased. In addition, skin conductance (indicating hydration of skin surface) significantly increased at the test cream sites compared to before application and to the placebo (Masako et al., 2005b).

11.4.6 Odor Management for Fungating Wounds

Fungating wounds may be caused by primary skin carcinomas, underlying tumors or via spread from other tissues. The malodor associated with such necrosis is caused by the presence of aerobic and anaerobic bacteria. The wounds rarely heal and require constant palliative treatment, leading to social isolation of the patients and poor quality of life.

Smell reduction with essential oils was first reported by Warnke et al. (2004) in 25 malodorous patients with inoperable squamous cell carcinoma of the head and neck. A commercial product containing eucalyptus, grapefruit, and tea tree essential oils (Megabac®) was applied topically to the wounds twice daily. Normal medication apart from Betadine disinfection was continued. The smell disappeared completely within 2-3 days and signs of superinfection and pus secretion were reduced in the necrotic areas.

Megabac has also been used in a small pilot study (10 patients) to treat gangrenous areas, being applied via spray thrice daily until granulation tissue formed. The treatment was then continued onto newly formed split skin grafts. All wounds healed within 8 weeks and no concurrent antibiotics were used (Sherry et al., 2003).

Use of essential oils to reduce the smell of fungating wounds in 13 palliative care patients was detailed by another group the following year. Lavandula angustifolia, Melaleuca alternifolia, and Pogostemon cablin essential oils were used alone or in combinations at 2.5-5% concentrations in a cream base. The treatments were effective (Mercier and Knevitt, 2005).

A further study was conducted with 30 patients suffering incurable head and neck cancers with malodorous necrotic ulcers. A custom-made product (Klonemax®) containing eucalyptus, tea tree, lemongrass, lemon, clove, and thyme essential oils was applied topically (5 mL) twice daily. All patients had a complete resolution of the malodor; in addition to the antibacterial activity, an anti-inflammatory effect was also noted (Warnke et al., 2006).

The use of essential oils to treat malodorous wounds in cancer patients is becoming widespread in many palliative care units although no formal clinical trials have been conducted as yet.

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