Written by Karen Pilkington and the CAM-Cancer Consortium.
Updated September 11, 2013

Ozone therapy

Does it work?

Systematic reviews, meta-analyses

No systematic reviews of ozone therapy in relation to cancer have been published. Systematic reviews have been published on other uses, for example, in the field of dentistry and in herniated discs.22,23

Narrative reviews

A series of narrative reviews have been published subsequently by researchers from Italy summarising the findings of their own research on ozone therapy.2,12,15,24 One review focuses on ozone therapy in cancer but primarily addresses pre-clinical research and a hypothesis related to restoration of normoxia in neoplastic growth.15 One study in chemotherapy-resistant cancer patients was described (further details below).

Clinical trials

No randomised controlled trials have been conducted to assess the effects of ozone therapy in cancer patients.

Early studies in cancer patients reported effects of ozone therapy on various parameters. In 40 patients with gynaecological cancer, ozone therapy was reported to cause a statistically significant decrease in levels of fatty acids and triglycerides.25 A second early study, in 21 women with progressive cervical cancer (Stages III and IV), assessed the effect of ozone autohaemotherapy in addition to conventional radiotherapy on immunological status.26 Small differences in IgG, IgA and IgM were observed but changes were not statistically significant.

More recently, an open study of ozone therapy in chemotherapy-resistant cancer patients was initiated in 2003.15 Preliminary findings revealed that, in patients with a Karnofsky performance score of less than 40% (on a scale of 0 to 100% where 0 represents death and 100% reflects normal activity/function and no evidence of disease), no effect on disease progression was observed. Patients with a Karnofsky score of 70% or less reported an improvement in quality of life after 30-45 treatments. The lack of a control group and subjective nature of the outcome measure prevent definitive conclusions being reached, a point conceded by the researcher.

Results of a pilot study of ozone therapy for tumour oxygenation were published in 2004.27 Eighteen patients with metastases or advanced tumours accessible to physical examination were enrolled in the study. All patients had a Karnofsky performance status of > 70%, 15 were male and 14 had head and neck tumours, 2 had gynaecological tumours and 2 had bone metastases in the chest wall. Ozone autohaemotransfusion was administered on 3 alternate days in one week. Tumour oxygenation levels were measured using needle probes. No overall statistically significant change was observed. Oxygenation did, however, improve in the most hypoxic tumours and no adverse effects were recorded. Due to the small sample size and uncontrolled nature of the study, these can only be considered preliminary findings. In addition, the clinical relevance of the observed changes in tumour oxygenation is not entirely clear although tumour hypoxia has been reported to adversely affect prognosis in tumours such as those of the head and neck tumours.28,29

A further study by this research group from Spain focused specifically on patients with advanced head and neck tumours who were undergoing radiotherapy.30 Nineteen patients were recruited and studied over a 3 year period. Twelve patients received chemotherapy in addition to radiotherapy while 7 received ozone therapy plus radiotherapy. The two groups were not well-matched as the ozone therapy group was older with greater lymph node involvement. However, no significant difference in overall survival was recorded between the two groups. The researchers suggest that it is possible that ozone therapy had a beneficial effect but it is also possible that the study was too small to detect a difference in outcome between the two groups.

Ozone has been investigated for other uses in cancer patients. These include the treatment of obstructive jaundice in 90 patients with gastro-intestinal tumours.31 A single case report described intravesical instillation of ozonized water in a patient with progressive radiation-induced haematuria.32 Another report suggested possible beneficial effects in prevention of postoperative gastrointestinal ulcers in 86 colorectal cancer patients.33 Osteonecrosis of the jaw has also been reportedly managed with treatments including ozone in myeloma patients (n=12, 34 and n=1, 47) as well as a separate series of 10 patients with bone metastases.35 The most recent report is a preliminary findings on the effects of ozone by rectal insufflations and/or by local application of ozonized-oil, in 19 patients with severe and/or refractory radiation-induced hemorrhagic proctitis.36 To date, none of these preliminary findings have been confirmed with randomised controlled trials.

Pre-clinical studies

Animal studies

Studies involving ozone-oxygen in animal cancer models have been conducted since the 1970s.37 One recent study involved peritoneal insufflations of an ozone/oxygen gas mixture compared with oxygen in rabbits with squamous cell carcinomas at an advanced stage. More rabbits in the ozone group survived and showed tumour regression and absence of lung metastases. The mechanism of action was unclear.38 A further animal study suggested that pre-treatment with intraperitoneal ozone reduce tissue damage in the ileum due to the cytotoxic agent, methotrexate.39

In-vitro studies

A series of in-vitro studies have shown effects such as a dose-dependent inhibition of the growth of human cancer cells from lung, breast, and uterine tumours,40 a potential radiosensitising effect and selective cytotoxic action on ovarian carcinoma cells,41 inhibition of proliferation of human neuroblastoma cells,42 a synergistic effect of ozone with 5-fluouracil43 and inhibition of the proliferation of neuroblastoma cells.44

Citation Karen Pilkington, CAM-Cancer Consortium. Ozone therapy [online document]. http://ws.cam-cancer.org/The-Summaries/Other-CAM/Ozone-therapy. September 11, 2013.


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