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Claims of benefits of aromatherapy for cancer patients include reduced anxiety levels and relief of emotional stress, pain, muscular tension and fatigue. The objective of this paper is to provide an updated descriptive, systematic review of evidence from pre-clinical and clinical trials assessing the benefits and safety of aromatherapy for cancer patients. Literature databases such as Medline (via Ovid), the Cochrane database of systematic reviews, Cochrane Central were searched from their inception until October 2010. Only studies on cancer cells or cancer patients were included. There is no long lasting effect of aromatherapy massage, while short term improvements were reported for general well being, anxiety and depression up to 8 weeks after treatment. The reviewed studies indicate short-term effects of aromatherapy on depression, anxiety and overall wellbeing. Specifically, some clinical trials found an increase in patient-identified symptom relief, psychological wellbeing and improved sleep. Furthermore, some found a short-term improvement (up to 2 weeks after treatment) in anxiety and depression scores and better pain control. Although essential oils have generally shown minimal adverse effects, potential risks include ingesting large amounts (intentional misuse); local skin irritation, especially with prolonged skin contact; allergic contact dermatitis; and phototoxicity from reaction to sunlight (some oils). Repeated topical administration of lavender and tea tree oil was associated with reversible prepubertal gynecomastia.
Aromatherapy encompasses the use of essential oils derived from different types of plant sources for a variety of application methods. Generally, the whole fresh plant (not crushed or powdered) is used for the essential oil distillation process. The specific ingredients of an essential oil are derived from plant materials or parts that are claimed to possess therapeutic properties. Essential oils are “the steam distillate of aromatic plants” (Tisserand and Balacs, 1995). They have been described as “the volatile, organic constituents of fragrant plant matter and contribute to both flavor and fragrance and are extracted either by distillation or by cold pressing (expression)” (Tisserand and Balacs, 1995). The history of distillation of essential oils started with the medieval physician Avicenna (Abu Ali al-Hussein Ibn Abdallah Ibn Sina; 980 – 1037) from Persia who invented the process of distillation and was probably the first to distil oil of the rose plant (Tisserand, 1988). Today, approximately 40 different oils derived from plants are used in aromatherapy. Lavender, rosemary, eucalyptus, chamomile, marjoram, jasmine, peppermint, lemon, ylang ylang, and geranium are some of the most popular.
The term ‘aromatherapy’ was coined by French chemist and perfumiér René Maurice Gattefossé in the 1920s and is a subcategory of ‘herbal medicine’ (Gattefosse, 1993). Gattefossé's book was published in 1937. He suggested that aromatherapy could be used to treat diseases in virtually every organ system, citing mostly anecdotal and case-based evidence. In the 1960s, aromatherapy was revived by the French homeopath Dr. Maury, and in the 1980s it increased in popularity in the United States. It is fairly well-established in Australia, Canada, France, Germany, New Zealand, Switzerland and the UK.
There are various forms of application. Most commonly, oils are applied topically in diluted forms, often together with a carrier oil as part of massage therapy to manipulate the soft tissue of the body, or by using an incense burner for inhalation of the aroma. Essential oils may be inhaled by adding a few drops to steaming water, thereafter an atomizer or humidifier spreads the aroma throughout the room. Certain aromatherapy oils are also ingested through teas, whereas others can be added to bathwater or pillows, or used to make ointments, creams and compresses. Some aromatherapists argue that the use of certain herbs in food can also be considered part of aromatherapy, although this should be considered as a specific alimentation rather than a precise use as essential oils.
Essential oils are supposed to improve physical and emotional wellbeing (www.cancer.gov/cancertopics/pdq/cam/aromatherapy/healthprofessional.page1). A wide range of claims for the effect of certain oils have been put forward, ranging from: to affect a patient's “subtle body”; bring balance to a distinct “chakra”; restore harmony to the “energy flow”; become centered; contribute to “spiritual growth”; alter mood and improve overall health; to more specific claims such as having anticonvulsive and spasmolytic properties (www.skepdic.com/aroma.html). It has been suggested that the topical application of aromatic oils may exert antibacterial, anti-inflammatory, and analgesic effects.
For cancer patients, claims of benefits include reduced anxiety levels and relief of emotional stress, pain, muscular tension and fatigue (Fellowes et al, 2004). Some of these alleged outcomes are vaguely defined.
The chemical properties and composition of a specific type of oil gives it whatever therapeutic qualities the essential oil might have. A number of theories try to explain the mechanism of action of aromatherapy and essential oils. The most often cited is the proposed connection between olfaction and the limbic system in the brain as the basis for the effects of aromatherapy on mood and emotions (Smith, 1999). These assertions have been contested by the biochemistry and psychology communities, which take a different view of the possible mechanism of action of odors on the human brain and do not differentiate the odors produced by essential oils from those of synthetic fragrances (Perry and Perry, 2006). Little is said about proposed mechanisms for its effects on other parts of the body. Unfortunately, many of these assumptions are primarily theoretical because of the lack of significant research addressing this topic. There is also a lack of in-depth neurophysiological studies on the nature of olfaction and its link to the limbic system.
An individual's expectation and subjective perception of oil supposedly influences treatment outcomes, including whether or not an individual has previous experience with a particular scent and whether it is perceived as pleasurable (www.sirc.org/publik/small.pdf). Marked association of odors with emotional response has been shown to be due to the prominence of afferent links from the olfactory bulb to the amygdala, where emotional significance is attached to incoming stimuli (Clark and Boutros, 1999).
Neuro-chemical aspects involve a suggested inhibition of glutamate binding, γ-amiobutyric acid (GABA) augmentation and acetylcholine receptor binding. As an example, the main terpenoid component of lavender oil is linalool. Linalool has been shown to inhibit glutamate binding in rats (Watt, 1995) and inhaled lavender oil reduces electroshock-induced convulsions in mice, which suggests augmentation of GABA (Yamada et al, 1994). Linalool's inhibitory effect was demonstrated to be dose dependent with increasing concentrations; all response was abolished by the use of 6.5 mM linalool. This modifying effect on the glutamatergic system is comparable with phenobarbital, a known anticonvulsant (Elisabetsky et al, 1995). Further evidence for this mechanism comes from the finding of a potentiation of GABA receptors expressed in Xenopus oocytes by lavender oil components (Aoshima et al, 2001).
It has been suggested that compounds from essential oils may enter the body (via the olfactory mucosa or the bloodstream by lung absorption) and may directly influence the brain (Watt, 1995). It is suggested that there are scent receptors in the nose which send chemical messages via the olfactory nerve to the brain's limbic region. This in return can affect a person's emotional responses, heart rate, blood pressure and breathing.
Generally speaking, the application of aromatherapy is suggested to help patients cope with stress, chronic pain, nausea and depression. One can assume both direct effects of the oils, but also positive expectations of the patients. Furthermore it has been suggested that the use of essential oils can relieve bacterial infections (Geda, 1995), stimulate the immune system (Komori et al, 1995), help to fight colds, flues and sore throats (Hasani et al, 2003), improve urine production (Morimoto and Shibata, 2010), increase circulation (Shiina et al, 2008) and aid in the healing of cystitis (Eriksen, 2000), herpes simplex (Buckle, 2002), acne (Eriksen, 2000), headaches (Eriksen, 2000), indigestion (Schnaubelt, 1999), premenstrual syndrome (Eriksen, 2000), muscle tension (Lis-Balchin et al, 2000), and even cancer (Fellowes et al, 2004). Specific indications can only be discussed by choosing a selected number of essential oils.
In Australia, three surveys showed that up to 1% of cancer patients used aromatherapy (Girgis et al, 2005, Salminen et al, 2004, Correa-Velez et al, 2003). In Canada, two surveys revealed that up to 4% of cancer patients used it (Tough et al, 2002, McKay et al 2005). In Italy, Spain and Turkey prevalence ranges from <1 to 2% (Johannessen et al, 2008, Fernandez-Ortega et al, 2008, Akyuz et al, 2007). In contrast, six surveys carried out in the UK showed that 40.6% of cancer patients were using it (Lewith et al., 2002, Maher et al., 1994, Rees et al., 2000, Harris et al., 2003, Scott et al., 2005, Shakeel et al., 2008). A US survey revealed that 11% of cancer patients may be using aromatherapy and in New Zealand 6% (Lawsin et al., 2007, Chrystal et al., 2003). However, it is unclear whether this usage is a specific anti-cancer intervention or simply to increase general well-being and thus life-style associated rather than a therapeutic approach. One could assume that a similar percentage of healthy individuals is using essential oil, too.
Since aromatherapy can also be applied orally or rectally, the administration of such oils may not be legally permitted in several countries, unless it is applied by a medically qualified person. There may be legal issues resulting from the fact that diluted essential oils can “penetrate the skin”, which could be considered as administering a drug. This review was carried out as a project for the European CAM cancer consortium (www.cam-cancer.org) and includes studies which assess the effect of aromatherapy on its own or in conjunction with massage therapy. The objective of this paper is to provide an updated review of evidence from pre-clinical and clinical trials assessing the benefits and safety of aromatherapy for cancer patients.
Literature databases such as Medline (via Ovid), the Cochrane database of systematic reviews, Cochrane Central were searched from their inception until October 2010. The main search terms were ‘aromatherapy’ AND ‘cancer’. For specific literature search procedures see Table 1 (OVID) and Table 2 (Cochrane Central and Cochrane database of systematic reviews). As this review was supposed to be comprehensive, we decided to also include results from pre-clinical studies on cancer cells. Thus, studies on cancer cells or cancer patients were included. The quality of publications was assessed by looking at the internal validity (study design and conduct), external validity (applicability and generalizability of results) and summarizing the direction of evidence (positive, uncertain, negative).
Yim et al (2009) carried out a systematic review specifically including trials for aromatherapy for depression (Yim et al., 2009). They included six studies applying aromatherapy massage in patients with depression. Three of the included studies evaluated the benefit of Swedish massage (two with lavender oil) for depressive symptoms of patients with cancer (mainly women with breast cancer). Results showed significant short term-improvement in anxiety and/or depression compared with usual care. No effect sizes were described. According to the authors this might be explained by an induction of a relaxation response in the autonomic nervous system. However, there was no adequate control intervention (i.e., massage without essential oils), and thus the relevance of this finding remains elusive.
All clinical studies which applied essential oils with or without massage to cancer patients were included. For the data selection process see flow diagram. A total of 18 clinical studies have been included in this review (Barclay et al., 2006; Chang 2008; Corner et al., 1995; Evans, 1995; Graham et al., 2003; Gravett, 2001a,b; Hadfield, 2001; Imanishi et al., 2009; Kirshbaum 1996, Kite et al., 1998, Louis & Kowalski 2002, Maddocks-Jennings et al., 2009, Soden et al., 2004, Stringer et al., 2008, Wilcock et al., 2004; Wilkinson et al., 1999; Wilkinson et al., 2007). Nine are randomised controlled studies (Barclay et al., 2006; Chang 2008; Corner et al., 1995; Maddocks-Jennings et al., 2009; Soden et al., 2004; Stringer et al., 2008; Wilcock et al., 2004; Wilkinson et al., 1999; Wilkinson et al., 2007), two are controlled (Graham et al., 2003; Louis and Kowalski 2002), three are uncontrolled (Gravett, 2001a,b; Hadfield, 2001) and four are case series (Evans, 1995; Imanishi et al., 2009; Kirshbaum, 1996; Kite et al., 1998) (see Table 3). The evidence of these trials points to a short-term benefit of aromatherapy / essential oils which could possibly last up to 2 weeks with reduction in anxiety and depression scores, improved sleep and an overall increase in wellbeing. Some of these trials also found an increase in patient-identified symptom relief and psychological wellbeing. However, other trials did not report any significant difference between groups. Since the comparator interventions used in the included trials vary greatly, it is not possible to assess the system and component efficacy of specific essential oils. The quality of publications ranged from mediocre to low. Double-blinding is practically impossible in the field of aromatherapy.
In conclusion, existing evidence provides weak evidence that aromatherapy might have some short-term effects on anxiety and depression, and possibly on pain relief. However, it is unclear whether this is a matter of positive expectation or a pharmacologically mediated effect.
There is considerable published research available on the in vivo and in vitro anti-inflammatory, anti-oxidant, antibacterial, antifungal, and antiviral activity of a number of essential oils. Furthermore, the cytotoxic, free radical scavenging, carcinogenetic, apoptosis inducing and anti-neoplastic effects of a number of essential oils has been investigated in pre-clinical trials (Gould, 1997). For a summary of the selected pre-clinical studies see Table 4 (Abe et al., 2003; de Sousa et al., 2004; Legault et al., 2007; Ait Mbarek et al., 2007a, b; Horvathova et al., 2007; Atsumi et al., 2007; Banerjee et al., 1994; Li et al., 2004; Xiao et al., 2008; Paik et al., 2005; Crowell et al., 1992). However, the concentrations applied in the respective studies might not be comparable to those in conventional aromatherapy, either volatile or directly resorbed.
It is generally accepted by aromatherapists that a safe and effective dilution for most aromatherapy/essential oils in massage therapy is a maximum of 2.5 % for adults, which translates to 2 drops of essential oil per 100 drops of carrier oil (2% dilution: 10–12 drops of essential oil per ounce of carrier oil). For full-body baths, the dosage of essential oil is usually 5–10 drops per bath. As long as practitioners know how to dilute them, non-toxic essential oils used on the skin are unlikely to harm the patient.
The testing of essential oils for safety has shown minimal adverse effects. A number of oils have therefore been approved for use as food additives and are classified as GRAS (generally recognized as safe) by the U.S. Food and Drug Administration (US Food and Drug Administration). There is, however, a risk involved with ingestion of large amounts of essential oils. For instance, severe, extensive, life threatening phototoxic reactions, such as the case of a woman who died of a massive phototoxic skin reaction, have been described after ingestion of food and medication containing psoralen and subsequent exposure to artificial UV radiation (Kaddu et al., 1998).
Some essential oils (e.g. camphor oil) can cause local irritation. The main safety issue with essential oils seems to be that cases of contact dermatitis have been reported, mostly in aromatherapists who have had prolonged skin contact with oils in the context of aromatherapy massage. In a mailed 2004 survey including members of a national massage therapy organization in the greater Philadelphia region found that the 12-month prevalence of hand dermatitis in subjects was 15% by self-reported criteria and 23% by a symptom-based method (Crawford et al., 2004). This problem had also been reported much earlier in the UK (Bilsland and Strong, 1990).
It has been suggested that since fragrance ingredients are still major causes of allergic contact dermatitis, the concentration of essential oils and materials with unknown composition can be problematic (Jansson and Loden 2001). Moreover, phototoxicity may occur when essential oils (particularly citrus oils) are applied directly to the skin before sun exposure (Kaddu 2001). Individual psychological associations with odors may result in adverse responses, especially if the memory of a scent provokes strong emotions (Holmes and Ballard 2004).
Repeated exposure to lavender and tea tree oils by topical administration was shown in one study to be associated with reversible prepubertal gynecomastia (Henley et al., 2007). The respective effect appears to have been caused by the purported weak estrogenic and antiandrogenic activities of lavender and tea tree oils. Therefore, these two essential oils could cause problems in patients with estrogen-dependant tumors. A review on the safety assessment of St John's Wort (Hypericum perforatum) oil concluded that the available data are insufficient to support the safety of ingredients from this plant in cosmetic formulations (Anonymous, 2001).
Findings on the interventional use of aromatherapy in cancer patients suggests a short-term benefit to reduce anxiety and depression, improve sleep and increase overall wellbeing; this effect has been suggested to last up to 2 weeks. Some of the trials also found an increase in patient-identified symptom relief and psychological wellbeing. However, other trials did not report any significant difference between groups. Since the comparator interventions used in the included trials vary greatly, it was not possible to make an easy assessment regarding the system and component efficacy of specific essential oils. Although there were some RCT, the quality of publications ranges from mediocre to low. In particular, double-blinding as a quality marker of clinical trials is nearly impossible in trials in the field of aromatherapy, and thus study quality tends to be lower compared to conventional pharmacological trials. Moreover, adequate control interventions are needed. For example, massage therapy generally has a positive effect on the recipient and most positive effects discussed above stem from trials that in adjunction apply essential oils. Thus, it is difficult to be certain as to where exactly the reason for a positive effect lies. However, wellbeing and offering these effects in a package are of limited harm and thus some cancer clinics or other voluntary organizations now offer aromatherapy or aromatherapy massage free of charge or at a lower cost.
The cost of essential oils varies depending on the quality, i.e. what part of the plant the oil is extracted from and which method that was used to extract it. Oils may be purchased from a licensed aromatherapist. For instance, essential oil from rose petals retails at €100 per ounce (appr. 28 grams) - based on the 110 pounds (50 kg) of rose petals needed for a single ounce of essential oil. Other plants retail at much lower prices as they yield more essential oil (for instance lavender, lemon, and eucalyptus). Lavender can be bought at €22 per ounce. Treatments of aromatherapy usually are priced from €40 to €75 for a 90 minute session.
The number of theories that try to explain the mechanism of aromatherapy can be categorized into psychological aspects and neuro-chemical effects. Proposed mechanisms claim effects on the limbic and olfactory system, which in turn is suggested to have an effect on mood (Diego et al., 1998). However, only very limited research confirms effectiveness or mechanism of action and in-depth studies have yet to shed sufficient light on these possible mechanisms and the connection between the olfactory and limbic system. Proponents of essential oils / aromatherapy also believe that the effects these oils have on the body are greater than the sum of the individual components of the scents (Perry and Perry, 2006). Furthermore, there are various discussions amongst aromatherapists as to whether natural oils are superior to synthetic ones. Currently, there are no references to scientific studies of the issue.
The limitations of this descriptive, systematic review include the fact that despite modern search engines and well-organized literature databases sometimes it is impossible to identify all the ‘grey literature’ regarding one topic. Thus, it is possible that the one or other study or case series is not included in this review. For instance, the medical search engine EMBASE was not searched. Furthermore, outcome measures and study designs of included studies varied to an extent that meta-analyzing the data was omitted due to heterogeneity.
As providers of essential oils are numerous and widespread in countries where aromatherapy is practiced, mainly on the European, North American, Australasian and Asian continents, comparability in trials with the same substance still may result in different outcomes. Moreover, training of aromatherapists and courses offered by some colleges and schools do not have a concerted curriculum which also includes a potential source of bias.
In summary, the use of diluted essential oils has minimal risks. Prolonged topical application may nevertheless cause allergic contact dermatitis. Repeated exposure to lavender and tea tree oils by topical administration was shown in one study to be associated with reversible prepubertal gynecomastia. Thus, patients with estrogen-dependant tumors should exercise caution. Aromatherapy/essential oils may be used safely by cancer patients for a short-term benefit in regard to reducing anxiety and depression symptoms and to increase sleep patterns and wellbeing.
We would like to thank the reviewers, Petter Viksveen and all the steering committee members of the European CAM cancer consortium for their valuable contribution to this piece of research. A small grant (€ 1250) was received by KB from the European CAM cancer consortium for carrying out the review.