Kwon HH, Yoon JY, Park SY, Min S, Suh DH. 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. October 2014;229(2):102-109.
Acne is an extremely common skin condition, particularly among adolescents. Although prescription medications can be effective in treating mild to moderate acne, they may cause adverse effects such as burning and antibiotic resistance. Tea tree (Melaleuca alternifolia, Myrtaceae) essential oil (TTO), obtained by steam distillation of the tree's leaves and twigs, is often used to treat acne and is reported to have efficacy similar to benzoyl peroxide, but also similar adverse effects. Used as a perfume, cosmetic, and disinfectant, hinoki false cypress (Chamaecyparis obtusa, Cupressaceae) contains compounds that have anti-inflammatory and antimicrobial activities. These authors performed a double-blind, randomized, controlled, spilt-face study to compare Lactobacillus-fermented C. obtusa (LFCO) and TTO for the treatment of mild to moderate acne and attempt to identify therapeutic mechanisms.
The study was conducted at Seoul National University Hospital in Seoul, South Korea, between January and July 2013. Thirty-four patients (11 males and 23 females) aged 25.9 ± 5.6 years with mild to moderate acne enrolled in the study. Exclusion criteria included pregnancy, mental illness, use of oral isotretinoin within 6 months, and use of any other acne medication within 6 weeks. Baseline evaluation revealed a mean Leeds acne grading score of 4.0 ± 1.2 on a scale of 0 to 10; 30.6 ± 10.6 inflammatory lesions; and 62.5 ± 52.5 noninflammatory lesions. The patients were instructed not to use any systemic, topical, or light-based acne treatments during the study.
All patients were randomly assigned to apply TTO cream to the acne lesions on 1 side of the face and LFCO to the lesions on the other side of the face twice daily for 8 weeks. The 2 creams had identical color and odor, and researchers as well as patients were blinded as to side-of-face assignment. Compliance was monitored by twice-weekly telephone interviews. At weeks 1, 2, 4, and 8, each patient underwent an acne evaluation, subjective assessment of improvement, and determination of sebum levels. Skin biopsies were taken from a random lesion at the beginning of the study and at a randomly selected time point for histological, immunochemical, and RNA-expression studies.
The creams, manufactured and supplied by BST Corporation (Sungnam, South Korea), were identical in formulation except in containing 5% TTO or 5% C. obtusa ferment filtrate. The ingredients of the creams were fully described in supplementary online material, as were fermentation methods for C. obtusa, of which raw material was purchased from a specified farm in South Korea.
Of the 34 enrolled patients, 32 followed and completed the entire study protocol, of which 2 skin biopsies were obtained from 25; no one dropped out of the study. The mean number of inflammatory acne lesions on the LFCO-treated side of the face significantly decreased by 16.5% (from 17.6 to 14.7 lesions, P<0.05) after 1 week of treatment and ultimately decreased by 65.3% (to 6.1 lesions, P<0.01) after 8 weeks. On the TTO side, inflammatory lesions were reduced by 24.7% after 4 weeks (from 17.0 to 12.8 lesions, P<0.05) and by 38.2% (to 10.5 lesions, P<0.01) after 8 weeks. At 2 weeks of treatment and thereafter, the reduction in inflammatory lesions was significantly greater with the LFCO treatment compared with the TTO treatment (P<0.05).
The number of noninflammatory lesions significantly decreased on the LFCO side (38.1%, P<0.01) after 4 weeks of treatment, but only after 8 weeks of treatment with TTO (23.7%, P<0.01). By week 8, the number of noninflammatory lesions on the LFCO side had decreased by 52.6% (P<0.01) compared with baseline. Beginning in week 4, a significant difference in noninflammatory lesion counts was observed between the 2 treatments (P<0.05).
Beginning at 2 weeks, statistical differences in Leeds acne grade at each time point were observed for the LFCO and TTO sides, with greater improvement seen with the LFCO treatment (P<0.05). Those changes were consistent with the changes in acne lesion counts. Acne grade on the LFCO side significantly decreased from 4.0 to 2.8 (P<0.01) at week 2 and to 1.8 at week 8. Acne grade on the TTO side decreased from 4.0 to 2.9 (P<0.01) at week 8.
Subjective satisfaction among all patients improved, with significant differences seen in favor of the LFCO treatment from week 2 (P<0.05). No severe adverse effects were reported. With the TTO treatment, 4 patients reported mild dryness and 6 reported mild redness and peeling. With the LFCO treatment, 2 patients reported dryness and 2 reported transient mild redness.
During the study, a tendency toward a decrease in sebum output from baseline was observed on the LFCO side; the TTO side did not show any significant change. After 8 weeks, the decrease in sebum output on the LFCO side was significant compared with baseline and compared with changes on the TTO side (P<0.05). Compared with baseline, a significant decrease in the overall size of the sebaceous glands was observed on the LFCO side (P=0.03); no change was seen on the TTO side.
Skin biopsies taken from lesions in 15 patients were examined with hematoxylin and eosin stains and immunohistochemistry analysis, and those from 10 patients were subjected to semiquantitative RNA-expression analysis. At week 1, improvement in histology grade was seen only on the LFCO side, and nuclear factor ĸB protein expression decreased only on the LFCO side. At 8 weeks, the expression of other proteins related to inflammation was reduced on both sides, with greater reductions seen on the LFCO side.
Ultra-performance liquid chromatography/high-resolution mass spectrometry demonstrated that compounds tentatively identified as dihydroxybenzoic acid, taxifolin 3-O-β-D-xylopyranoside, and quercetin 3-rhamnoside increased in LFCO after fermentation. An in vitro bioassay further showed that solid-fermented LFCO was much stronger than TTO in inhibiting Propionibacterium acnes, the bacterium linked to acne, though a water extract of C. obtusa was inferior.
Examining which bioactive compounds might be responsible for the apparent mechanisms of action, the authors observe that both TTO and hinoki false cypress contain compounds with known antimicrobial and anti-inflammatory activities. Earlier literature reporting that the common practice of fermentation may increase antimicrobial activity in other, unrelated plants also was cited.
Among the limitations of this study are the lack of a control group receiving no treatment, the small number of patients and particularly the small number of skin biopsies available for each time point, and the inclusion of only Korean patients. The authors suggest that their results "provide valuable information for the discovery of new natural anti-acne compounds," but they could certainly also inform the development of botanical products.
This study was supported by the 2012 Asian Acne Board Research Grant and Seoul National University Hospital Research Fund.―Shari Henson