Twenty-three studies with more than 1,634 participants were included in the review.
There were methodological flaws in the majority of the included studies.
Tea tree oil.
One RCT compared tea tree oil water-based gel with 5% benzoyl peroxide lotion. The tea tree oil was significantly less effective than benzoyl peroxide in reducing inflammatory lesions, although it produced an improvement over baseline.
Nigerian Toto ointment and soap.
One RCT compared Toto ointment and soap with sulphur ointment. It reported that participants showed good response to Toto ointment or soap, or to both.
Ocimum gratissimum oil and Ocimum basilicum leaves; Aloe vera. Three studies examined products containing Ocimum gratissimum oil or Ocimum basilicum. One reported that three of 16 Ocimum gratissimum oil products produced a significantly greater reduction in lesion count than a comparison treatment of 10% benzoyl peroxide. A second study found that Ocimum gratissimum oil combined with 50% and 100% Aloe vera was superior to placebo. A methodologically poor study found that topical application of Ocimum basilicum leaves were as effective as oral tetracycline combined with topical sulphur.
A double-blind, placebo-controlled, crossover RCT found that linoleic acid reduced follicular size in patients with comedonal acne. However, this was not a study of efficacy on clinical acne. A second study of uncertain design claimed a 75% reduction in inflammatory acne lesions with linoleic acid, but no supporting data were presented.
Gluconolactone and glycolic acid.
A double-blind, placebo-controlled trial found that topical gluconolactone was significantly more effective than placebo in the reduction of both inflammatory and non-inflammatory acne lesions. Its efficacy was comparable to 5% benzoyl peroxide for non-inflammatory lesions, but was significantly lower for inflammatory lesions. It was less irritating to the skin than benzoyl peroxide. An RCT found that 70% glycolic acid was as effective as Jessner's solution and was better tolerated. An RCT that compared 15% topical glycolic acid combined with azelaic acid with topical tretinoin found a significantly greater reduction in inflammatory lesions after 12 weeks, but no difference in comedones. Two uncontrolled studies reported improvement of acne with self-administered glycolic acid before and after physician-administered glycolic acid peels, but statistical support for this was not provided.
Ayerverdic herbal formulations.
Three RCTs assessed ayervedic herbal formulations. One double-blind trial found that topical and oral ayervedic herbal formulations were effective treatments and suggested that combined treatment was superior to oral treatment alone. A second trial found one of four Ayervedic oral therapies to be significantly superior to placebo. The final trial found that two Ayervedic preparations were superior to a third.
A small unblinded RCT compared oral gugulipid with oral tetracycline and found it to be equally effective.
Mask containing several Chinese ingredients.
A poor-quality uncontrolled study reported that a regimen involving a salve and a mask containing several Chinese drugs produced improvement or cure in 83.2% of participants.
Compound oldenlandis mixture.
An incompletely reported study found an oral compound olenlandis mixture to be superior to pills containing Chinese Angelica and Flavescent Sophora.
Chinese-Japanese Kampo formulations.
One controlled trial compared oral administration of one of three Kampo formulations (Seijo-bofu-to, Jumi-haidoku-to, and Toki-shakuyuka-san) to one of two antibiotics. The Kampo formulations were reported to be as effective as the antibiotics and to be superior in the treatment of incidental symptoms, the clinical significance of which was not clear.
Japanese shark liver and gallbladder extract (isolutrol).
A double-blind RCT comparing isolutrol with benzoyl peroxide was performed, but only before-and after results for each intervention were reported. Isolutrol significantly reduced inflammatory but not non-inflammatory lesions in mild to moderate acne.
An uncontrolled study of oral pyroxidine for premenstrual acne flares found that 72% of participants felt the intervention attenuated symptoms, 19% that it did not, and 9% were unsure. This was a self-assessed retrospective outcome measure.
Two poor-quality before-and-after studies examined vitamin A. One of these used 50,000 IU twice daily and found the majority of patients' symptoms were unchanged; the other used 300,000 IU daily and reported that the majority of patients showed a good or excellent response.