Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling side effects of cancer treatment. It develops after certain chemotherapy drugs - including platinum compounds, taxanes, vinca alkaloids and bortezomib - damage peripheral nerves, causing numbness, tingling, burning pain and loss of sensation, usually in the hands and feet. CIPN can force dose reductions or early stopping of chemotherapy, and for many patients the symptoms persist long after treatment ends. A key driver of this nerve damage is oxidative stress: an imbalance between reactive oxygen species and the body's antioxidant defences that injures nerve cells. Despite how common CIPN is, there are currently very few treatments that reliably prevent or reverse it.

Study design

This paper is a narrative review, not a clinical trial with new patient data. The authors - a multidisciplinary Spanish and international research team - brought together existing evidence on the biological mechanisms of CIPN, the role of oxidative stress in nerve damage, and the proposed mechanisms of medical ozone therapy. They examined how controlled, low-dose ozone exposure interacts with the body's antioxidant and anti-inflammatory systems, drawing on preclinical studies and a small number of earlier clinical reports. The stated purpose of the review was to lay out the scientific rationale and background for a planned randomised clinical trial testing ozone therapy in CIPN, which the authors note was already underway at the time of writing.

Findings

The evidence reviewed suggests that, when administered at controlled therapeutic doses, ozone can trigger an adaptive response in the body's own antioxidant systems (a hormetic effect) rather than simply adding further oxidative burden. The authors describe a limited number of experimental and small clinical reports indicating this antioxidant modulation could plausibly help protect nerves affected by chemotherapy. However, the authors are explicit that this proposed benefit had not yet been confirmed in a properly controlled trial at the time of publication - the paper presents a hypothesis and supporting mechanistic evidence, not a demonstrated clinical effect.

What the authors concluded

The authors concluded that current options for preventing or treating established CIPN remain extremely limited, and that the mechanistic evidence for ozone's antioxidant and anti-inflammatory action provides a reasonable scientific basis to test it formally. They stated that appropriately controlled ozone therapy is a plausible adjuvant approach worth investigating, and that a randomised clinical trial to establish its potential benefit in CIPN was needed - and already in progress.

Limitations of this study

As a narrative review, this paper does not present new patient outcome data and cannot itself demonstrate that ozone therapy works for CIPN. Its conclusions rest on preclinical research and a small number of earlier clinical reports, many with limited sample sizes and study quality, rather than a large, controlled trial. Narrative reviews are also more prone to selective emphasis than systematic reviews. The randomised clinical trial the authors describe as the next step had not reported results at the time this paper was published. This study concerns chemotherapy-induced peripheral neuropathy, a side effect of cancer treatment. It does not establish ozone as a treatment or cure for cancer itself. Ozone therapy is a complementary approach and should always be discussed with your oncology team.