Complementary and alternative medicines such as oil of melaleuca have become increasingly popular in recent decades. This essential oil has been used for almost 100 years in Australia but is now available worldwide both as neat oil and as an active component in an array of products. The primary uses of oil of melaleuca have historically capitalized on the antiseptic and anti-inflammatory actions of the oil. This review summarizes recent developments in our understanding of the antimicrobial and anti-inflammatory activities of the oil and its components, as well as clinical efficacy. Specific mechanisms of antimicrobial and anti-inflammatory action are reviewed, and the toxicity of the oil is briefly discussed.

Many complementary and alternative medicines have enjoyed increased popularity in recent decades. Efforts to validate their use have seen their putative therapeutic properties come under increasing scrutiny in vitro and, in some cases, in vivo. One such product is oil of melaleuca (TTO), the volatile essential oil derived mainly from the Australian native plant Melaleuca alternifolia. Employed largely for its antimicrobial properties, TTO is incorporated as the active ingredient in many topical formulations used to treat cutaneous infections. It is widely available over the counter in Australia, Europe, and North America and is marketed as a remedy for various ailments.

TTO is composed of terpene hydrocarbons, mainly monoterpenes, sesquiterpenes, and their associated alcohols. Terpenes are volatile, aromatic hydrocarbons and may be considered polymers of isoprene, which has the formula C5H8. Early reports on the composition of TTO described 12, 21, and 48 components. The seminal paper by Brophy and colleagues examined over 800 TTO samples by gas chromatography and gas chromatography-mass spectrometry and reported approximately 100 components and their ranges of concentrations.
Given the scope for batch-to-batch variation, it is fortunate that the composition of oil sold as TTO is regulated by an international standard for “Oil of Melaleuca—terpinen-4-ol type,” which sets maxima and/or minima for 14 components of the oil. Notably, the standard does not stipulate the species of Melaleuca from which the TTO must be sourced. Instead, it sets out physical and chemical criteria for the desired chemotype. Six varieties, or chemotypes, of M. alternifolia have been described, each producing oil with a distinct chemical composition. These include a terpinen-4-ol chemotype, a terpinolene chemotype, and four 1,8-cineole chemotypes. The terpinen-4-ol chemotype typically contains levels of terpinen-4-ol of between 30 to 40% and is the chemotype used in commercial TTO production. Despite the inherent variability of commercial TTO, no obvious differences in its bioactivity either in vitro or in vivo have been noted so far.