Accepted Manuscript

Aromatherapy, Botanicals, and Essential Oils in Acne

Warren Winkelman

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DOI: doi:10.1016/j.clindermatol.2018.03.004
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AROMATHERAPY, BOTANICALS, AND ESSENTIAL OILS IN ACNE

Warren Winkelman, MD, PhD1

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Nestlé Skin Health Investigation, Education, Longevity Development (SHIELD), New York,

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NY

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Corresponding author: Warren Winkelman, MD, PhD; Senior Medical Director and Head of

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Medical Innovation, Nestle Skin Health Investigation, Education, and Longevity Development

(SHIELD), New York, NY; phone: 1-646-495-3045; email: warren.winkelman@galderma.com

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Key words: Acne, essential oil, complementary and alternative medicine, aromatherapy
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Disclosures: W. Winkelman is an employee of Nestle Skin Health Investigation, Education, and

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Longevity Development (SHIELD), a sister company of Galderma Laboratories, LP which

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markets an over-the-counter acne product containing an essential oil.

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Abstract word count: 97

Word Count (excluding refs): 1872

Figures: 4

Tables: 1

References: 29

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ABSTRACT

Complementary and alternative medicine approaches are popular among some patient segments

due to the perception that they are “natural” and thus are believed to be less likely to be

dangerous, to have less toxic, or to cause side effects. In dermatology, these can include

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aromatherapy, botanicals, and essential oils (plant extracts). Preliminary evidence, biological

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activity studies, and small pilot clinical trials conducted outside of North America, mostly in

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young adults, suggest that some may have value in acne treatment. When additional research

and larger clinical trials are conducted, both clinicians and patients will be able to understand

the risks/benefits compared with allopathic remedies.

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INTRODUCTION

Acne is one of the most common dermatologic diseases and can affect individuals from early

adolescence through adulthood.1-3 Both the primary lesions of acne (papules, pustules,

comedones) and the secondary lesions (post-inflammatory hyperpigmentation, erythema, and

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scarring) can cause considerable psychosocial impact, regardless of the patient’s age.4

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Complementary and alternative medicine (CAM) is popular with patients and consumers in

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many areas of medicine, including dermatology,5 largely because they are perceived to be more

“natural” than allopathic prescriptive medicines, and thus they are believed to be less toxic and

safer with fewer side effects.6

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The terms “complementary” and “alternative” refer to different concepts – “alternative” is use of

a non-mainstream therapeutic approach instead of allopathic prescription and over-the-counter

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medications, while “complementary” is use of non-mainstream therapies together with allopathic

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medications.5 Patients may anticipate that these therapeutic approaches go beyond the

minimization of their symptoms, potentially “boosting” their immune systems or promoting their
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general wellness.5 In dermatology, common CAM approaches can include topical agents
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(generally plant extracts), essential oils/aromatherapy, herbal therapy, and acupuncture.5

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While few CAM approaches have received rigorous evaluation in terms of Western medicine,

particularly in children or adolescents,5 there have been some investigations into use of CAM for

management of acne This review focuses on the use of essential oils and aromatherapy in acne.

Existing evidence for CAM therapies has come from small pilot studies; in some cases, more

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research with larger controlled clinical trials is warranted in the evaluation of the effectiveness of

complementary therapy for acne.7

CLARIFICATION OF RELEVANT TERMS

When discussing essential oils and aromatherapy, “botanicals” is a somewhat nonspecific term,

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referring to most plant-based chemicals (phytochemicals) and may describe complex plant

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extracts, containing many chemical moieties or pure single compounds.8, 9 Examples of single

compound botanicals well-known in dermatology include psoralens, capsaicin, indigo, and

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podophyllin. Two complex polyphenol phytochemical botanicals studied for acne therapeutics

include green tea extract and aloe vera leaf oil.10-12

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The term “essential oils” refers to botanicals that are volatile plant extracts with distinctive scents

(i.e., the so-called “essence” of the plant). Essential oils may be used in a variety of ways, such
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as mixed in a gel, compounded into a paste or spray, or applied via bath, massage, or inhalation
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(Fig. 1). These oils are believed to be absorbed through the upper dermis. Aromatherapy refers to

the therapeutic use of aromatic essential oils.8, 9

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The United States Food and Drug Administration (FDA) distinguishes cosmetics from drugs, and

essential oils can be considered either depending on intended use. According to FDA, cosmetics

are “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or

otherwise applied to the human body … for cleansing, beautifying, promoting attractiveness, or

altering the appearance.” The FDA definition of a drug is: “articles intended for use in the

diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food)

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intended to affect the structure or function of the body of man or other animals.”13 Under the

FDA framework, categorization of essential oils refers to a fragrance marketed for promoting

attractiveness as a cosmetic but those marketed with certain “aromatherapy” claims, such as

reducing the number of acne lesions or improving acne, meet the definition of a drug. Similarly,

a massage oil intended to lubricate skin and impart fragrance would be considered cosmetic;

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however, one marketed for relieving skin irritation is considered a drug.

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INSIGHTS FROM THE LITERATURE

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Mechanisms of action

There are several theories of how aromatherapy can achieve therapeutic effects; proposals
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include systemic effects (acting as drug or enzyme), placebo effects, or general affective or
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“reflectorial” effects that induce positive moods.14

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Multiple organic compounds are present in essential oils and have differing therapeutic actions
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(Table 1).9 Essential oils typically comprise multiple natural volatile organic compounds and

can be extracted from almost any plant part; for example, eucalyptus and peppermint oil are
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extracted from leaves, lavender and rose oils from flowers, juniper and sandalwood from woody

parts of the plant, vetivert and calamus from the roots, and benzoin and frankincense oils from

sap.9 These oils often include a mixture of many organic compounds with therapeutic properties,

which reflect relative amounts of each compound contained in the oil.9 Wound healing

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properties occur with oils high in ketones, but antimicrobial/anti-infectious properties are

associated with oils high in alcohols.9

Essential Oils and Aromatherapy as Alternative Therapy for Acne

Tea Tree Oil (TTO)

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The essential oil derived from the plant Melaleuca alternifolia is known as tea tree oil and has

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been used medicinally in some countries for many decades.15 Unlike many other botanicals, TTO

has been well characterized and standardized to an international standard.16 Most tea tree oil

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marketed in the USA contains approximately 100 terpenes, with the most abundant (40%) being

terinen-4-ol. TTO demonstrates broad-spectrum antimicrobial activity via non-specific cell

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membrane damage.17-19 It is an ingredient in many over-the-counter products for acne (face/body
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washes/cleansers, soaps, toners, treatment gels or lotions, blemish sticks, masks).20 An evidence-

based review of botanicals for dermatologic use showed that TTO “may have potential to
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become standard treatment” for acne.21

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Several clinical studies of TTO have been performed in acne; in a single-blind study, 124
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subjects with mild to moderate acne were given either 5%TTO or 5% BPO.22 There were
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significant reductions in inflammatory and comedonal lesions with both treatments. TTO had a

slower onset of action but better tolerability than BPO.22 In a randomized 45-day controlled trial

of 5% TTO vs vehicle in 60 subjects with mild to moderate acne,, TTO when applied twice

daily for 20 minutes and then rinsed off with water, was superior to vehicle in reducing total,

inflammatory, and non-inflammatory lesions (Fig. 2). In addition, TTO was well tolerated,

although a small proportion of patients experienced pruritus, burning, and scaling.16

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Unfortunatly, a recent Cochrane analysis judged the evidence supporting use of TTO to be of

low quality23 due to methodologic and reporting limitations, notably of the aforementioned

study.23

Lactobacillus Fermented Chamaecyparis obtusa (LFCO) Leaf Extract

Chamaecyparis obtusa is a species of cypress that grows in Asia and is widely used in the

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cosmetic industry. Fermentation of C obtusa by Lactobacillus fermentum yields an extract that

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has strong inhibitory effects on Propionibacterium acnes. In a 2014 study of an 8-week

randomized, controlled split face study to compare LFCO with TTO 5% (n=34 subjects with

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mild to moderate acne,24 inflammatory lesions were reduced by 65.3% with LFCO compared to a

38.2% reduction with TTO (Fig. 3). A faster onset of action was documented with LFCO
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(P<.05) and a greater effect on inflammation and inflammatory markers (Fig. 4). In addition to
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the effect on inflammatory lesions, LFCO was also associated with diminished non-
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inflammatory lesions (52.6%, p<.05). LFCO was sebosuppressive and associated with a

reduction in size of sebaceous glands, with concomitant lower sebum output. While both
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treatments resulted in significant reductions in acne lesions, LFCO was superior. The authors of

the report compared the rapid onset of action to that of topical retinoids and antibiotics,
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suggesting that LFCO “might partly overcome the side effects” associated with traditional acne
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medications.

Copaiba

Copaiba is a stimulating oleoresin obtained from the trunk of varieties of the South American

tree genus Copaifera.25 It has been used for centuries in Central and South America, particularly

in Brazil where it is considered a “skin-healing agent.”25 The oil-resin is used in traditional

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medicine for its anti-inflammatory, healing, and antiseptic qualities . The therapeutic actions of

Copaiba are primarily attributed to diterpine compounds in the oil which serve the plant as

biologica defenses against predators and pathogens.25 In a 21-day double-blind study of Copaiba

essential oil versus placebo in patients with mild inflammatory acne, assessments utilized

standardized photographs and analysis of area occupied by acne pustules.25 There was a

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decrease of the acne lesions in the affected areas affected in both treated and control regions.25

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Unfortunately, it is very difficult to compare changes in the acne lesions with traditional acne

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studies due to the use of non-standardized outcome measures.

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Essential Oils and Aromatherapy as Complementary Therapy in Acne
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Sandalwood oil

Sandalwood oil is used as a therapeutic agent in many Asian countries to treat inflammatory and
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cutaneous eruptions. 26, 27 It has antibacterial actions against S aureus, S epidermidis, and P acnes
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at concentrations of 0.06% and lower.26 Anti-inflammatory effects are thought to occur via

inhibition of COX-1 and -2 and 12-lipoxygenase pathways, as well as in lipo-polysaccharide

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stimulated dermal fibroblasts and keratinocyte models.26 Another model employed synthetic
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sandalwood induced wound healing in human keratinocytes.28 Recently, sandalwood oil 0.5%

was formulated with salicylic acid for evaluation in acne patients. An 8-week open-label study
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involved 42 subjects with mild to moderate acne who were treated with a four part regimen of

0.5% salicylic acid with sandalwood in a cleanser, serum, spot-treatment, and mask. Subjects

used the cleanser twice daily morning and night, applied the serum after cleansing, had the

option of using spot treatment on individual blemishes up to 3-4 times per day, and employed a

mask 3 times per week. 89% of subjects showed disease improvement versus baseline as rated

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on global assessment scores. Mean decreases in inflammatory lesions were 37%, non-

inflammatory lesions 25%, and total lesions 31%. The products were generally well tolerated,

with burning, dryness and stinging being the most common treatment-related complaints.26

Rosemary Extract

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Rosemary extract contains at least three bioactive compounds: rosmarinic acid, carnosol, and

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carnosic acid.29 These have different modulatory effects on cytokine production. In vivo mouse

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models have shown inhibition of P acnes induced inflammation via inhibition/suppression of

cytokine production. Additionally, rosemary extract may reduce NF-kB activation and normalize

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TLR-2 in vitro.29 While the addition of rosemary extract may contribute anti-inflammatory
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actions to cosmeceutical or dermatologic products,29 injection of rosemary extract is not

associated with skin irritation or inflammation in the mouse model.

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Jeju Essential Oil

Jeju essential oil is derived from Thymus plants.30 Jeju essential oil may have antibacterial
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activities with effects against P acnes,30 according to a 2009 study, where the researchers suggest
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the agent may be useful for treating acne patients..

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Korean Citrus

Citrus oils from Citrus obovoides and Citrus natsudaidai have been tested for antibacterial

activity against P acnes and S epidermidis.31 Results showed lower P acnes secretion of IL-8 and

TNF-a, suggesting potential utility in acne.31

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CONCLUSIONS

Currently, there is weak clinical evidence that TTO 5% may be used as an alternative acne

therapy. Several agents may be helpful as complementary therapy, due to biologic plausibility

but little clinical evidence. There is as yet no proof of psychosocial outcome effectiveness, cost-

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effectiveness, or any other economic advantages, and no insights into impact on post-

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inflammatory hyperpigmentation in patients with darker skin tones. Despite the lack of

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evidence, dermatologists would be served well to at least understand complementary and

alternative remedies, when their patients ask about such agents and their potential clinical value

in the management of their acne.

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ACKNOWLEDGEMENTS
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Valerie Sanders assisted in the preparation of the manuscript.

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REFERENCES
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1) Dreno B, Poli F. Epidemiology of acne. Dermatology. 2003; 206:7-10.

2) Dreno B, Layton A, Zouboulis CC, et al. Adult female acne: a new paradigm. J Eur Acad
AC

Dermatol Venereol. 2013; 27:1063-1070.

3) Gollnick HP, Finlay AY, Shear N, et al. Can we define acne as a chronic disease? If so,

how and when? Am J Clin Dermatol. 2008; 9:279-284.

4) Koo JY, Smith LL. Psychologic aspects of acne. Pediatr Dermatol. 1991; 8:185-188.

Winkleman p 10
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5) Cirik V, Efe, E. The use of complementary and alternative medicine in children. J Fam

Med Community Health. 2015; 2:1031-1034.

6) Kemper KJ, Vohra S, Walls R, et al. American Academy of Pediatrics. The use of

complementary and alternative medicine in pediatrics. Pediatrics. 2008; 122:1374-1386.

7) Sawni A, Singh A. Complementary, holistic, and integrative medicine: acne. Pediatr Rev.

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2013; 34:91-93.

IP
8) Agnew T, Leach M, Segal L. The clinical impact and cost-effectiveness of essential oils

CR
and aromatherapy for the treatment of acne vulgaris: a protocol for a randomized controlled trial.

J Altern Complement Med. 2014; 20:399-405.

9)
US
Stevensen CJ. Aromatherapy in dermatology. Clin Dermatol. 1998; 16:689-694.
AN
10) Mahmood T, Akhtar N, Khan BA, et al. Outcomes of 3% green tea emulsion on skin

sebum production in male volunteers. Bosn J Basic Med Sci. 2010; 10:260-264.
M

11) Fowler JF, Jr., Woolery-Lloyd H, Waldorf H, et al. Innovations in natural ingredients and
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their use in skin care. Journal of drugs in dermatology : JDD. 2010; 9:S72-81; quiz s82-73.

12) Chularojanamontri L, Tuchinda P, Kulthanan K, et al. Moisturizers for Acne: What are
PT

their Constituents? J Clin Aesthet Dermatol. 2014; 7:36-44.

CE

13) Federal Food, Drug, and Cosmetic Act.

14) Kiecolt-Glaser JK, Graham JE, Malarkey WB, et al. Olfactory influences on mood and
AC

autonomic, endocrine, and immune function. Psychoneuroendocrinology. 2008; 33:328-339.

15) Hammer KA. Treatment of acne with tea tree oil (melaleuca) products: a review of

efficacy, tolerability and potential modes of action. Int J Antimicrob Agents. 2015; 45:106-110.

Winkleman p 11
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16) Enshaieh S, Jooya A, Siadat AH, et al. The efficacy of 5% topical tea tree oil gel in mild

to moderate acne vulgaris: a randomized, double-blind placebo-controlled study. Indian J

Dermatol Venereol Leprol. 2007; 73:22-25.

17) Carson CF, Riley TV. Antimicrobial activity of the major components of the essential oil

of Melaleuca alternifolia. J Appl Bacteriol. 1995; 78:264-269.

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18) Brand C, Ferrante A, Prager RH, et al. The water-soluble components of the essential oil

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of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human

CR
monocytes, but not neutrophils, activated in vitro. Inflamm Res. 2001; 50:213-219.

19) Koh KJ, Pearce AL, Marshman G, et al. Tea tree oil reduces histamine-induced skin

inflammation. Br J Dermatol. 2002; 147:1212-1217.

US
AN
20) Rosamilia LL. Over-the-counter treatments for acne and rosacea. Semin Cutan Med Surg.

2016; 35:87-95.
M

21) Reuter J, Merfort I, Schempp CM. Botanicals in dermatology: an evidence-based review.

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Am J Clin Dermatol. 2010; 11:247-267.

22) Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus
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benzoylperoxide in the treatment of acne. Med J Aust. 1990; 153:455-458.

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23) Cao H, Yang G, Wang Y, et al. Complementary therapies for acne vulgaris. Cochrane

Database Syst Rev. 2015; 1:CD009436.

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24) Kwon HH, Yoon JY, Park SY, et al. Comparison of clinical and histological effects

between lactobacillus-fermented Chamaecyparis obtusa and tea tree oil for the treatment of acne:

an eight-week double-blind randomized controlled split-face study. Dermatology. 2014;

229:102-109.

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25) da Silva AG, Puziol Pde F, Leitao RN, et al. Application of the essential oil from copaiba

(Copaifera langsdori Desf.) for acne vulgaris: a double-blind, placebo-controlled clinical trial.

Altern Med Rev. 2012; 17:69-75.

26) Moy RL, Levenson C, So JJ, et al. Single-center, open-label study of a proprietary topical

0.5% salicylic acid-based treatment regimen containing sandalwood oil in adolescents and adults

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with mild to moderate acne. Journal of drugs in dermatology : JDD. 2012; 11:1403-1408.

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27) Misra BB, Dey S. Comparative phytochemical analysis and antibacterial efficacy of in

CR
vitro and in vivo extracts from East Indian sandalwood tree (Santalum album L.). Lett Appl

Microbiol. 2012; 55:476-486.

28)
US
Busse D, Kudella P, Gruning NM, et al. A synthetic sandalwood odorant induces wound-
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healing processes in human keratinocytes via the olfactory receptor OR2AT4. J Invest Dermatol.

2014; 134:2823-2832.
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29) Tsai TH, Chuang LT, Lien TJ, et al. Rosmarinus officinalis extract suppresses
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Propionibacterium acnes-induced inflammatory responses. J Med Food. 2013; 16:324-333.

30) Oh TH, Kim SS, Yoon WJ, et al. Chemical composition and biological activities of Jeju
PT

Thymus quinquecostatus essential oils against Propionibacterium species inducing acne. J Gen
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Appl Microbiol. 2009; 55:63-68.

31) Kim SS, Baik JS, Oh TH, et al. Biological activities of Korean Citrus obovoides and
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Citrus natsudaidai essential oils against acne-inducing bacteria. Biosci Biotechnol Biochem.

2008; 72:2507-2513.

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Table 1. Organic compounds present in essential oils and their proposed therapeutic actions.

From Stevenson et al. Clin Dermatol. 1998;16:689-694.9

Organic Compounds Proposed Therapeutic Actions

Acids Anti-infectious, immunostimulants

Aromatic aldehydes Anti-infectious, immunostimulants

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C10 alcohols Anti-infectious, immunostimulants

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C15 and C20 alcohols Estrogen-like activity

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Aldehydes Anti-infectious,calming, litholytic

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Coumarins Balancing, calming

Esters Antispasmodic, calming

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Lactones Balancing, calming

Ketones Cicatrizing (wound healing), mucolytic, litholytic, calming

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Oxides Expectorant, antispasmodic

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Phenols Anti-infectious, immunostimulants

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Phenyl methyl esters Anti-infectious, antispasmodic

C10 terpenes Anti-infectious, cortisone-like activity

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C15 terpenes Antihistamines, anti-allergic

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Figure 1. Examples of essential oils and plants used to create essential oils. © Can Stock Photo /

duskbabe, with permission.

Figure 2. Effect of Tea Tree oil on acne severity index and total lesion counts (secondary

outcome measure). From Enshaieh S, et al, with permission.16

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Figure 3. (a) Changes in inflammatory acne lesion counts and (b) non-inflammatory lesion

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counts with LFCO and TTO. From Kwon et al, with permission.24

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Figure 4. Histologic analysis of skin. (a) H&E stain at baseline and 8 weeks with
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histophathologic inflammation scores at each visit shown in the graphs (inflammation around

sebaceous gland with acne lesion); (b, c) Immunohistochemical stain intensity from the LFCO
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side (b) and TTO side (c). (d) Semi-quantitative reverse transcription PCR analysis of frozen
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skin samples at baseline and week 8. *p<0.05. GAPDH = glyceraldehyde 3=phosphate

dehydrogenase. From Kwon et al, with permission.24

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