Ozone therapy is an alternative medical treatment in which ozone, a molecule made up of three oxygen atoms and which protects our planet from ultraviolet rays, is applied or introduced into the body to treat a variety of illnesses. Before we continue, it’s worth hearing what the American Food and Drug Administration has to say about ozone therapy:
Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy.Code of Federal Regulations
Not a great start, but let’s not dismiss ozone just yet. Absence of evidence isn’t evidence of absence after all, so we’ll give ozone therapy a fair hearing, but do keep the FDA’s words in mind as we proceed. Now let’s take a more detailed look – is there any research at all to suggest that ozone has untapped potential as a medical intervention?
Ozone is a molecule made up of three oxygen atoms and is naturally present in the Earth’s atmosphere, protecting us from harmful ultraviolet radiation from the sun. Despite being made from the same atoms, ozone is a very different beast when compared to good old O2. It’s a pale blue gas that smells a little like chlorine, and is much less stable than O2. It will readily lose one of its three oxygen atoms as superoxide (a highly reactive, negatively charged oxygen ion).
It’s the reactivity of ozone that resulted in its first effective application over 100 years ago as a disinfectant. Ozone oxidises and damages cell membranes and genetic material, and is quite effective at killing microorganisms. As a gas, it can reach tight spaces, and since it reacts to produce oxygen, it leaves no harmful residue.
Ozone is also a ‘secondary’ pollutant. Ozone is created when certain chemicals, such as those found in vehicle exhaust and industrial emissions, react with sunlight. In towns and cities, ozone concentrations can become high enough to have a negative effect on public health. Ozone pollution is linked to increased risk of respiratory diseases and can aggravate existing ones, as it causes airway inflammation.
So, while ozone in the upper atmosphere is good for our planet, direct exposure to ozone doesn’t seem very healthy. Why on Earth would you want to inhale, inject, or otherwise expose someone to ozone for medical purposes? Let’s take a look at some proposed uses and see if they hold water.
If ozone kills microorganisms, can it be used to help combat infection in humans? This idea isn’t new – during the 1st World War, German doctors used ozone to disinfect the wounds of soldiers. More recently, ozone has been proposed as a means of treating SARS-CoV-2 infections, either by infusing ozone directly into the blood, or by withdrawing blood and exposing it to ozone, then returning it into the patient’s circulation.
In order to effectively kill viruses, the concentration of ozone must be fairly high. This is a pretty significant problem, because ozone doesn’t discriminate between pathogens and human cells, and will damage both in equal measure. According to the FDA: ‘In order for ozone to be effective as a germicide, it must be present in a concentration far greater than that which can be safely tolerated by man and animals.’
Some have proposed that doses of ozone low enough to be safe could be beneficial in addition to conventional treatments for viral infections. This is because ozone may enhance the effectiveness of antiviral drugs by modulating the immune system and by attacking the proteins that viruses use to invade human cells.
There are some randomised, controlled trials suggesting that ozone therapy in conjunction with conventional treatment may improve COVID-19 outcomes. However, these trials are small and should be viewed with caution given the toxic nature of ozone.
There is no reliable human evidence to suggest that ozone therapy is beneficial for the treatment of any form of cancer. Ozone therapy as a cancer therapy is not approved by any respectable health authority, and tends to be offered by private oncology clinics, often alongside other forms of alternative medicine like homeopathy (one of the most rigorously debunked practices in all of medical science). As the saying goes, a medical treatment is known by the company it keeps.
The idea of using ozone to treat cancer is based on the Warburg effect – the observation that cancer cells consume more glucose (sugar) and less oxygen. This led to the (now outdated) idea that delivering oxygen and/or ozone (which breaks down into oxygen) to cancer cells might harm them. We now know this is false – high oxygen levels do not harm cancer cells any more than they harm regular cells. While some studies suggest that sufficient levels of ozone can harm cancer cells in culture (not surprisingly given its toxicity), there is no evidence that this can be done safely in humans. Indeed, since 2012, there have been at least 5 confirmed deaths related to oxygen or ozone therapy targeted at cancer. In 2016, American oncologist David Gorski (an outspoken critic of alternative medicine) described ozone therapy for cancer as ‘pure quackery’.
Given that ozone pollution is linked to respiratory disease, it should come as no surprise that inhaling ozone deliberately is a pretty bad idea. In human tissues, ozone produces reactive oxygen species (ROS), primarily hydrogen peroxide. Followers of this site will probably be familiar with ROS – molecules that quickly react with lipids, proteins and DNA, damaging them and increasing the strain upon a cell’s repair machinery. ROS also contributes to inflammation, a key driver of most age-related diseases. Sufficient ozone inhalation can cause lung inflammation and pulmonary oedema (fluid filling the lungs) within a few hours of exposure.
The interior of the lungs are not very well protected against ROS in comparison to the rest of the body’s tissues. It has been suggested that when introduced into the circulation in carefully controlled amounts, ozone could act as a hormetic. A hormetic treatment is one that is beneficial at low doses, but becomes harmful at higher doses. When exposed to ROS, cells up their defensive game, increasing the activity of genes coding for antioxidants – the molecules that protect cells by neutralising ROS. Another possible hormetic effect of low ROS exposure is a suppression of important inflammatory molecules. Because of these mechanisms, it has been suggested that ozone could paradoxically be beneficial in preventing and treating inflammatory conditions.
Unfortunately, this is not really supported by human evidence so far. In 2020, a meta-analysis of 6 randomised, controlled trials of ozone therapy for knee osteoarthritis found it to be no more effective than hyaluronic acid, which itself is barely more effective than a placebo treatment. Another systematic review the same year concluded that trials of ozone therapy were generally biased and of poor quality. A similar picture emerges for chronic back pain, multiple sclerosis and other chronic inflammatory diseases: where evidence does exist to support ozone therapy, it’s generally of poor quality, with small clinical trials either lacking a placebo control or not having a control group at all.
Ozone has been proposed as a treatment for some cardiovascular diseases. This is once again based on ozone’s potential ability to affect the immune system and inhibit inflammation, with inflammation being an important factor in many cardiovascular diseases. It has also been proposed that, as in the case of ozone therapy for cancer, ozone in combination with oxygen could allow higher delivery of oxygen to areas where blood circulation is restricted, in this case accelerating the healing process.
There is currently little human evidence to support a benefit for ozone therapy in cardiovascular disease. Few clinical trials exist, and those that do are small and are often not randomised or placebo-controlled. It’s also worth noting that there are reports of ozone therapy causing coronary thrombosis.
Exposure to ozone pollution has been linked to increased risk of dementia. Some have proposed that ozone therapy could have the opposite effect by reducing oxidative stress and inflammation in the brain, which is thought to be a driver of neurodegeneration. This is again reliant on a hormetic effect of ozone when delivered to tissues at low levels.
One study found that ozone reduced amyloid beta production and improved cognition in a mouse model of Alzheimer’s disease. However, there does not appear to be any human data showing that ozone therapy is helpful for people with dementia.
Some less well-studied therapies have genuine medical applications, but may be falsely appropriated for conditions in which there is not sufficient evidence to support their effectiveness. Ozone therapy does not seem to fall into this category – as the FDA states, there is currently no known useful medical application for this treatment, though evidence could emerge in the future to suggest otherwise.
Title image by Andrei Lazarev on Upslash
Ozone therapy in COVID-19: A narrative review: https://doi.org/10.1016/j.virusres.2020.198207
Oxygen Therapy: https://web.archive.org/web/20100721031010/http://www.cancer.org/Treatment/TreatmentsandSideEffects/ComplementaryandAlternativeMedicine/PharmacologicalandBiologicalTreatment/oxygen-therapy
German alternative cancer clinics: Combining experimental therapeutics with rank quackery and charging big bucks for it: https://sciencebasedmedicine.org/german-alternative-cancer-clinics/
Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review: https://doi.org/10.3390%2Fijms23052528
The Effect of Ozone (O3) versus Hyaluronic Acid on Pain and Function in Patients with Knee Osteoarthritis: A Systematic Review and Meta-Analysis: https://doi.org/10.22038/abjs.2020.46925.2292
Oxygen-Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials: https://doi.org/10.1016/j.arthro.2019.05.043
Myocardial Infarction after Ozone Therapy: Is Ozone Therapy Dr. Jekyll or Mr. Hyde?: https://doi.org/10.1159/000431078
Ozone Inhibits APP/Aβ Production and Improves Cognition in an APP/PS1 Transgenic Mouse Model: https://doi.org/10.1016/j.neuroscience.2019.07.027