Effectiveness of Ozone Therapy as an Adjunct Treatment for Lower-Limb Ulcers: A Systematic Review

Background: chronic lower-limb ulcers are slow to heal

Chronic ulcers of the lower limbs, including venous leg ulcers and diabetic foot ulcers, are among the most difficult wounds to heal. They can persist for months, cause considerable pain and reduced mobility, raise the risk of infection and amputation, and place a heavy burden on patients and health services. Standard wound care does not always achieve closure, so researchers have explored additional therapies. Ozone has been studied as one such adjunct, applied topically to the wound, because of its proposed antimicrobial and tissue-repair actions.

Study design: seven studies pooling 506 patients

This paper is a systematic review of the published literature on ozone therapy for lower-limb ulcers. The authors searched for clinical studies in which ozone was used alongside conventional wound care in adults aged 18 years or older who had chronic wounds of the lower limbs, such as venous or diabetic ulcers. Seven studies met the inclusion criteria, together enrolling 506 patients. The majority of these studies focused on diabetic foot ulcers. The ozone protocols varied across the included studies, covering different delivery methods, concentrations and treatment schedules.

Findings: healing effect reported across all included studies

Across the seven studies reviewed, the ozone therapy protocols were associated with a healing effect on the ulcers, and none of the studies reported adverse effects attributable to the treatment. The reviewers noted that this pattern was consistent across the included studies, although the underlying trials differed in design, ozone protocol and how outcomes were measured.

What the authors concluded

The authors concluded that ozone therapy showed a positive healing effect when used as an adjunct for lower-limb ulcers, with no reported adverse effects in the studies reviewed. They were careful to frame this as encouraging rather than definitive, stressing that more controlled and randomised clinical trials are needed to confirm effectiveness and to establish clear clinical criteria for how and when ozone should be used.

Limitations of this study

As a systematic review, the strength of its conclusions depends on the quality of the underlying studies, and here that evidence was limited. Only seven studies were available, several were small, and the ozone protocols, wound types and outcome measures varied widely, which makes direct comparison and pooling difficult. Diabetic foot ulcers were over-represented, so the findings may not apply equally to venous or other lower-limb ulcers. The absence of reported adverse effects should be read with caution, because small studies are not designed to detect uncommon harms. The authors themselves highlight the shortage of well-controlled, randomised trials, meaning these results are best seen as a promising signal that needs stronger confirmation before firm clinical recommendations can be made.