Table 1.
Characteristics, main results, and limitations of the included studies focusing on acne. Details about the composition of the preparations are given in Table S1 (Supplementary Materials).
| Author(s) (Publication Year; Country) | Study Design (n) | Intervention (n) | Control (n) | Outcome Measure(s) | Study Duration (Evaluation Period) | Main Results | Limitations |
|---|---|---|---|---|---|---|---|
| Enshaieh et al. (2007; Iran) [36] | Randomized, double-blind, and placebo-controlled study (60) | 5% TTO 1 in carbomer gel (30) | Carbomer gel (30) | —Total lesion count —ASI 2 —Number of comedones, papules, and pustules —Monitoring ADRs 3 |
45 days (baseline and every 15-day period) | —After treatment, a significant reduction in the mean TLC 4, ASI 2, and the numbers of comedones, pustules, and papules in the intervention group was observed but not in the control group (significant difference) —5 patients reported minimal pruritus, 3 patients reported a little burning sensation, and 1 patient reported minimal scaling (divided over the intervention and placebo groups) |
—Short duration of study and follow-up time —Small sample size |
| Kwon et al. (2014; South Korea) [37] | Prospective double-blind, randomized, and controlled split-face trial (34) | 5% Lactobacillus-fermented Chamaecyparis obtusa (LFCO) in cream (34) | 5% TTO 1 in cream (34) | —Acne grade —(Non-)Inflammatory lesion count —Histopathology and immunohistochemistry of lesions —Patients’ subjective assessment —Average size of sebaceous glands —Sebum secretion —Monitoring ADRs 3 |
8 weeks (baseline; 1, 2, 4, and 8 weeks) | —A significant difference between both groups in inflammatory lesion counts and acne grading was observed after 2 weeks and for non-inflammatory lesion counts after 4 weeks —A significant reduction in the overall size of the sebaceous gland was observed on the lactobacillus side when compared to the baseline, but not on the tea tree oil side —In the tea tree oil group, 4 patients reported mild dryness and 6 reported mild erythema and desquamation —In the lactobacillus group, 2 patients reported mild dryness and 2 reported dryness |
—Risk of cross-contamination —Lack of comparison to a control or placebo —Small sample size and all were Korean |
| Da Silva et al. (2012; Brazil) [38] | Double-blind and placebo-controlled clinical trial (10) | 1% Copaiba essential oil in natrozol gel (10) | Natrozol gel (10) | —Photographs to determine the total area occupied by acne | 21 days (baseline and weekly) | —After 21 days, a highly significant decrease in the extent of the area affected by acne was observed in both the placebo and intervention groups; however, the effect in the intervention group was greater —The results observed in the placebo group could not be explained, and aggravations occurred in most of the participants —The decrease in the surface area affected with acne in the intervention group can mostly be explained by the model |
—Short duration of study and follow-up time —Small sample size —Only one outcome —No safety assessment —No demographics reported |
| Bassett et al. (1990; Australia) [39] | Prospective and single-blind comparative study (124) | 5% TTO 1 in gel (61) | 5% benzoyl peroxide in lotion (63) | —Severity of acne (counting technique) —(Non-)Inflammatory lesion count —Oiliness, erythema, scaling, pruritus, and dryness —Monitoring ADRs 3 |
3 months (baseline and three times with monthly intervals) | —At the baseline, a greater facial erythema assessment was observed in the tea tree oil group compared to the benzoyl peroxide group —At 1, 2, and 3 months, benzoyl peroxide reduced a greater number of inflamed lesions compared to the tea tree oil group; however, the reduction in both groups was significant —There was not a significant reduction in non-inflamed lesions observed in both groups —79% of the benzoyl peroxide group reported ADRs 3, whereas 44% of the tea tree oil group reported ADRs 3 (a significant difference) |
—Lack of control or placebo group |
| Ghovvati et al. (2019; Iran) [40] | Open-label, assessor-blind, and uncontrolled clinical trial (20) | 0.5% cinnamon in gel (20) | NA | —(Non-)Inflammatory lesion count —Size and quantity of follicular fluorescence spots —Skin biophysical parameters —Monitoring ADRs 3 |
45 days (baseline; 4 and 8 weeks) | —ADRs to 1% cinnamon in gel were observed in 6 subjects; therefore, the 0.5% cinnamon in gel was used in this trial —After 8 weeks, significant reductions in the non-inflammatory and inflammatory lesion counts, sebum content, and erythema index were observed compared to the baseline —Non-significant changes were observed for the skin hydration and melanin index —13 patients reported mild burning and 11 patients reported facial redness after using the cinnamon gel |
—Lack of comparison to a control, placebo, or standard therapy —Short duration of study and follow-up time —Small sample size —No demographics reported |
| Talebi et al. (2020; Iran) [41] | Open-label, assessor-blind, and uncontrolled clinical trial (20) | 1% (w/w) ajwain in gel (20) | NA | —Digital and fluorescence photography —Biophysical skin profile measurement (stratum corneum hydration, sebum content, TEWL 5, erythema index, melanin, and pH value) —TLC 4 —VAS 6 —Monitoring ADRs 3 |
8 weeks (baseline; 4 and 8 weeks) | —After 8 weeks, a significant reduction in the total lesion count, non-inflammatory lesion count, and a mean decrease in the size and quantity of red spots was observed —After 8 weeks, the decreases in sebum and pH values were significant —No ADRs 3 were reported |
—Lack of comparison to a control, placebo or standard therapy —Small sample size |
| Malhi et al. (2017; Australia) [42] | Uncontrolled, dual-center, and open-label phase II pilot study (14) | 200 mg/g of TTO 1 gel and 7 mg/g of tea tree face wash (14) | NA | —IGA 7 score —TLC 4 —Skin oiliness —Frequency of ADRs 3 —Mean local tolerability score |
12 weeks (baseline; 4, 8, and 12 weeks) | —After 4, 8, and 12 weeks, a significant reduction in the TLC 4, IGA 7 score, and facial oiliness score was observed —Adherence was high, and no serious adverse events were reported |
—Lack of comparison to a control, placebo, or standard therapy —Short duration of study and follow-up time —Small sample size |
| Hassan et al. (2013; Saudi Arabia) [43] | Clinical trial (5) | Eucalyptus oil in cream (5) | NA | —Photographs —Outcomes not defined |
10 days (monitored routinely) | —All patients showed good results after the second week of treatment | —Lack of comparison to a control, placebo, or standard therapy —Short duration of study and follow-up time —Small sample size —No specific outcomes reported —No safety assessment |
| Najafi-Taher et al. (2022; Iran) [44] | Triple-blind and randomized clinical trial (100) | TTO 1 nano-emulsion in adapalene gel (53) | Adapalene gel (47) | —Number of (non-)inflammatory lesions —TLC 4 —ASI 2 —Monitoring ADRs 3 |
12 weeks (baseline; 4, 8, and 12 weeks) | —Number of (non-)inflammatory lesions, TLC 4, and ASI 2 showed a greater improvement in the intervention group compared to the positive control —Only mild ADRs 3 were reported in both groups, with dryness being the most common adverse effect |
—Lack of comparison to a control or placebo |
| Mazzarello et al. (2018; Italy) [46] | Single-center, randomized, and double-blind comparative study (60) | —Group A: 20% propolis, 3% TTO 1, and 10% Aloe vera (PTAC) in cream (20) | —Group B: erythromycin cream (20; positive control) —Group C: vehicle (20; placebo) |
—Cutaneous status —Macro-photography —Quantity of sebum —Skin surface pH —Cutaneous erythema index —Number of comedones, papules, and pustules —TLC 4 —ASI 2 |
30 days (baseline; 15 and 30 days) | —All the clinical and instrumental values studied were statistically different from the placebo group —The sebometry, pH, and erythema index values were not significantly different statistically during the treatment in the three study groups —The intervention of group A was more effective in reducing ASI 2 and TLC 4 compared to the intervention of group B —The interventions of both groups A and B showed a significant reduction in the number of (non-)inflammatory lesions |
—Short duration of study and follow-up time —No safety assessment |
| Mazzarello et al. (2020; Italy) [47] | Comparative randomized, single-center, and single-blind study (60) | 3.74% Myrtus communis L. essential oil, 0.1% Origanum vulgare essential oil, and 0.025% tretinoin (MOTC) in cream (30) | 1% clindamycin and 0.025% tretinoin (CTG) (30; cream) | —Amount of skin sebum, pH, erythema index, and TEWL 5 —Macro-photography —Number of comedones, papules, and pustules —TLC 4 —ASI 2 |
30 days (baseline; 15 and 30 days) | —All the instrumental values studied were statistically different between the two groups; however, no sebometry and pH changes were observed in both groups —The MOTC intervention was better than the CTG control in reducing the popular erythema index —In the CTG control group, erythema of the inter-papular healthy skin significantly increases statistically —Both products improved clinical parameters, and no statistically significant differences were detected between the groups |
—Lack of comparison to a placebo —Short duration of study and follow-up time —No safety assessment |
| Parveen et al. (2009; India) [48] | Controlled, randomized, and single-blind clinical trial (30) | Unani herbomineral in cream (20) | Vehicle of cream (10) | —IGA 7 | 60 days (baseline; 15, 30, 45, and 60 days) | —The IGA 7 means show a very significant difference between the baseline and day 15, day 30, day 40, and day 60 after treatment, whereas very significant differences in the placebo group were observed between the baseline and days 45 and 60 —No significant difference in the IGA 7 was observed between the baseline and days 15 and 30 in the placebo group |
—Lack of comparison to a standard therapy —No safety assessment —Low number of outcomes |
| Kim and Shin (2013; South Korea) [49] | Non-equivalent control group, pretest–post-test design (54) | A basic, weekly acne treatment and a dermal application of a mixture of 3% TTO 1 and 2% lavender oil in jojoba oil as the carrier (27) | Basic, weekly acne treatment (27) | —Acne-related characteristics —Number of P. acnes —Number of human skin pathogens —Number of acne lesions —Sebum secretion rates |
4 weeks (baseline and weekly) | —A significant reduction in the total number of P. acnes, the sebum excretion rate, and non-inflammatory skin lesions was observed in the intervention group but not in the control group —The number of human skin pathogens showed no significant difference in both groups —The number of acne lesions was significantly reduced in both groups |
—Short duration of study and follow-up time —Small sample size —No safety assessment |
| Orafidiya et al. (2002; Nigeria) [50] | Preliminary clinical tests (126; seven subjects per product) | Ocimum gratissimum leaf essential oil preparations (1% v/v polysorbate 80, cetomacrogol blend, and petrolatum base, or 50% v/v alcohol) (112) | —Reference: 10% benzoyl peroxide in lotion (7) —Placebo: 40% arachis oil in 1% v/v polysorbate 80 (7) |
—Number of comedones, papules, and pustules (acne lesion count) —Number of days taken to achieve a 50% reduction in lesion count —Skin sensitivity —Patient acceptability —Monitoring ADRs 3 |
4 weeks (baseline and weekly) | —The intervention products were significantly more effective in reducing lesions than the placebo —The effect of the reference treatment was gradual over the 9 days, being more pronounced in the later part of the treatment period —A burning sensation was the most reported adverse event within the intervention group —In the placebo group no adverse events were reported |
—Short duration of study and follow-up time —Small sample size in the different treatment groups —No demographics reported |
| Orafidiya et al. (2004; Nigeria) [51] | Preliminary clinical investigation (84; 12 subjects per product) | Ocimum gratissimum leaf essential oil preparations (lotion in 25% and 50% of aqueous aloe gel or 100% of aloe gel) (48) | —Reference/positive control: 1% clindamycin solution (12) —Negative control: Neat aloe gel dispersed in 1% polysorbate 80 (12) —Placebo: 40% of arachis oil emulsion in 1% v/v polysorbate 80 (12) |
—Number of comedones, papules, and pustules (acne lesion count) —Number of days taken to achieve a 50% reduction in lesion count —Skin sensitivity -—Patient acceptability —Monitoring ADRs 3 |
4 weeks (baseline and weekly) | —In the negative control group, minimal activity was observed —A greater reduction in the substant lesion counts was observed in the intervention group compared to the negative and positive control groups —The preparations containing a greater quantity of aloe vera showed greater improved outcomes —Stinging sensation on the skin was the most reported adverse event (96%), which was tolerable —Only mild skin irritation was reported within the intervention group |
—Short duration of study and follow-up time —Small sample size in the different treatment groups —No demographics reported |
| Hassoun et al. (2016; United States) [52] | Case study (1) | Cedarwood oil tretinoin cream (1) | NA | NA | 4 weeks (baseline and 4 weeks) | —After 4 weeks of treatment, the patients’ faces were clear and had rare open and closed comedones on the chest with no papules | —Lack of comparison to a control, placebo, or standard therapy —Combination preparation —Only one case —Retrospective study —Uncontrolled |
1 TTO: tea tree oil. 2 ASI: acne severity index. 3 ADRs: adverse drug reactions. 4 TLC: total lesion count. 5 TEWL: transepidermal water loss. 6 VAS: visual analog scale. 7 IGA: Investigator’s Static Global Assessment. Clinical trial registration numbers: Ref. [37]: NCT01930565 and Ref. [42]: NCT 01657110. NA = not applicable.