Rational Prescribing Article Series

Life on Earth would not be possible without ozone. High above us in the stratosphere, a layer of the atmosphere that is 15-35 km above the surface of our planet, trace amounts of ozone absorb most of the sun’s ultraviolet radiation. It is able to do this because it is very unstable, so it can neutralize these high-energy particles of light, stabilizing into oxygen in the process. This energy transfer is called oxidation, and it explains how ozone therapy works in your body.

Because it is a strong oxidant, ozone turns on your body’s antioxidant systems. Studies have reported changes in several antioxidants, and in enzymes, cytokines and other markers of inflammation after ozone therapy. Recent evidence suggests that one of the key mechanisms of action ozone involves NF-KB, a signalling molecules that turns on genes related to inflammation. One of these in particular, called Nrf2, actually turns on immune cells that stimulate tissue repair.

This summary of the evidence supporting ozone is heavy reading, but it reveals some important issues that can help you appreciate the complexity of evidence-based medicine. While it is important to use the most proven therapies first, many doctors assume that using less proven treatments is taboo. Regulators also frown on this, but one of the core values shared by many integrative MDs is a moral and ethical duty to help- patients whose suffering is not relieved by guideline-based care. Some purists might consider ozone therapy unproven, but it is definitely worth a trial.

There have been a handful of systematic reviews evaluating ozone therapy for osteoarthritis (OA) of the knee, with encouraging results. One of these found 12 trials that compared ozone to other therapies in a total of 858 patients with knee OA. The authors reported that the quality of these studies was generally poor, so no firm conclusions could be drawn, but that short- to medium-term pain relief was promising. Another reported on eight trials involving 718 patients with knee OA, reporting more convincing positive findings. In yet another review of six trials involving 467 patients with knee OA, weekly injections of ozone were comparable but slightly inferior to injections of hyaluronic acid.

The problem with these studies is that every trial used a different protocol for ozone therapy. Dose is measured in micrograms (μg) of ozone, and these trials used anywhere from 75 to 450 μg per injection with different volumes and concentrations.

Trials on knee OA are also complicated by the fact that most patients with knee pain actually have arthritis because of misalignment of the bones and soft tissues in the hip and thigh, the ankle and foot. These inevitably subject the knee joint to excessive pressure and strain. In these patients, treating the knee is like treating the flood in your basement without patching the leak in your roof.

Previous injuries in these areas can restrict movement, acting as blockages and points of tension. These are like knots in the long chains of fascia that hold us together. Amazingly, these blockages have not yet been described by medical science, so they are typically ignored by even the best sports medicine physicians and orthopedic specialists.

These blockages are important confounders; because in some of these trials, ozone was injected in the knee, but also around the knee. In patients who have blockages in these areas, this technique can be expected to improve results. Injecting blockages with ozone is a logical and rational approach to more targeted ozone therapy. Like many procedures, success with ozone depends just as much on the musician as on their instrument.

The same is true for low back pain, which has been treated with ozone for decades. The first studies used x-ray guidance to inject ozone directly into the spine. A systematic review of ozone injections into herniated discs reported consistently positive results. Another systematic review focused on trials that targeted the foramina or the paravertebral muscles, with ozone injections of different doses given over widely ranging dosing schedules. Ozone injections were better than a sham procedure, and were comparable to steroid injections.

Ozone also kills many bacteria and other pathogenic microbes on contact. This is one reason why its use has grown among biological dentists. A systematic review of 12 trials found that rinsing with ozonated water was promising for the treatment of dental caries, also called cavities. Ozone-based protocols are effective for osteonecrosis of the jaw, a rare but devastating side-effect of the bisphosphonates drugs that are used to treat osteoporosis. It provided no added benefit, however, to the standard root canal procedure or for nonsurgical periodontal disease of the gums.

Positive clinical trials of ozone have also been reported in systematic reviews that looked at all the different treatments for specific conditions. Topical ozonated water was effective for the treatment of lichen planus. Other studies have reported significant benefits in healing foot ulcers and other chronic wounds.