Ozone Therapy: A Deeper Review

Written by Devin Wilson, ND

RECAP OF OZONE THERAPY

Ozone therapy is a versatile treatment that involves the administration of medical grade ozone/oxygen gas via intra or periarticular injection, systemically via IV, topically and, bladder and rectal insufflation. Ozone therapy has multiple mechanisms of actions and diverse biological effects, and therefore can be used in the treatment of a wide range of conditions, including musculoskeletal, cardiovascular, infectious and degenerative. It is primarily used for its tissue regenerative, pain reducing, anti-oxidant, anti-inflammatory, anti-septic and immuo-stimulatory properties. Ozone therapy can be administered in different ways including Prolozone therapy, minor/major autohemotherapy, topical applications and others.

MECHANISMS OF ACTION OF OZONE THERAPY

Ozone therapy has a wide range of therapeutic uses along with an array of mechanisms of actions. It is thought to exert most of its therapeutic effects by activating various nuclear transcription factors. Ozone gas mixed with blood turns creates hydrogen peroxide and special messenger molecules called Lipid Ozonated Products or Alkenals which activate numerous transcription factors including nuclear factor erythroid 2 related factor (Nrf2), nuclear factor of activated T cells (NFAT), activated protein-1 (AP-1), hypoxia inducible factor-1 (HIF-1), etc. These transcription factors have a various functions and actions. See Below.

ozone MOA diagram.jpg

BRIEF REVIEW OF TRANSCIPRION FACTORS ACTIVATED BY OZONE THEREAPY

  • Nrf2 (nuclear factor erythroid 2 related factor) and ARE (antioxidant response element) reduce NFkB and stimulate the production of numerous antioxidant enzymes including Catalase, SOD, GPx, HO-1, HSP10 and others.

  • NFAT (nuclear factor of activated T cells) and AP-1(activated protein-1) modulate the immune system and reduce cytokine mediated inflammation.

  • HIF-1 (hypoxia inducible factor-1) increases VEGF, EPO and glycolytic enzymes and is implicated in Ozone’s versatility in treating cardiovascular and neurodegenerative diseases.

BIOLOGICAL RESPONSES AND EFFECTS OF OZONE THERAPY

Ozone increases oxygen saturation, improves blood flow and activates red blood cells…

Ozone therapy can raise the saturation of blood oxygen, improve blood circulation, activate the metabolism of red blood cells, and modify the degree of cerebral infarction ischemia. Ozone can also increase the content of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate in blood cells, promoting blood and oxygen supply.

Ozone also activates pentose phosphate pathway carbohydrate metabolism pathways to increase the production of nicotinamide adenine dinucleotide phosphate (NADP), which is important for the maintenance of red blood cell membrane integrity.

It was previously reported that ozone therapy caused a decrease in blood viscosity of peripheral anticoagulated whole blood, resulting in improved microcirculation and enhanced tissue activity to improve oxygen supply and renew cell function.

Ozone can improve platelet function…

Ozone can change the polymerization of blood platelets to improve blood clotting in patients with stroke. The production of hydrogen dioxide resolves the thrombus and decreases whole blood viscosity. Ozone and hydrogen dioxide also accelerate the circulation of tricarboxylic acid, increase basal metabolism, and promote catabolism of fat to remove fatty materials, including color spots attached to the vessel wall.

Ozone can improve circulation…

Ozone can improve blood circulation and blood flow patterns in arteries and veins to increase the flexibility of red blood cells, which increases blood flow through the capillaries and increases tissue oxygen supply.

Ozone can improve red blood cell metabolism…

Ozone provides ATP to hypoxic-ischemic brain tissue. For cells with an active metabolism acting via the pentose phosphate pathway, pentose phosphate pathway mainly provides the energy in the form of nicotinamide adenine dinucleotide phosphate (NADP) of the monooxygenase system. NADP is the coenzyme for glutathione reductase, and is critical for the maintenance of red blood cell membrane integrity. After ozone therapy, the ATP content in blood cell also increases, indicating improved blood cell metabolism. Major ozonated autohemotherapy can maintain ATP and energy metabolism in brain tissues under conditions of ischemia and hypoxia, resulting in a decrease in cellular apoptosis.

Ozone eliminates free radicals…

Ozone activates anti-oxidase enzymes and eliminates free radicals. It is well established that the mechanism of cerebral ischemia, especially cerebral edema and tissue damage caused by cerebral ischemia-reperfusion, is closely related to mass production of oxygen free radicals. It has been reported that the protective effect of ozone was strongly associated with nitric oxide production following increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase. The protective effect of ozone was also suggested to involve upregulation of the antioxidant defense system and beneficial effects on blood circulation and oxygen metabolism. Finally, ozone preconditioning has a protective effect against skeletal bone ischemia/ reperfusion injury by decreasing levels of malondialdehyde and protein carbonyl, and increasing activities of superoxide dismutase and glutathione peroxidase.

BIOLOGICAL RESPONSES AND EFFECTS OF OZONE THERAPY SUMMARY…

  • Supports tissue repair by enhancing the release of numerous growth factors

  • Improves oxygen delivery in ischemic tissue due to nitrous oxide production

  • Increases levels of intra-erythrocytic 2, 3-DPG which improve oxygen exchange

  • Decreases blood viscosity which improves circulation

  • Up-regulates free radical scavengers such as glutathione peroxidase, catalase and superoxide dismutase

  • Upregulates cellular antioxidant enzymes and induction of HO-1 and HSP70

  • Supports and modulates the immune system and reduces cytokine mediated inflammation

  • Increases production of ATP

  • Maintains RBC membrane integrity by activating the pentose pathway

  • Reduces chronic inflammation and chronic pain

  • Does not procure acute or late side effects

  • Procures a surprising wellness in most patients, probably via the stimulation of the neuroendocrine system

  • Activates neuroprotective systems

HOW DOES PROLOZONE THERAPY WORK?

Prolozone therapy is the combination of prolotherapy and ozone therapy. A small volume of Ozone gas is injected into tendons, ligaments, joint capsules and joint spaces following prolotherapy injections. Ozone therapy further supports tissue repair by improving oxygen delivery to damaged or injured tissues, improving circulation, stimulating a cascade of growth factors including platelet derived growth factor (PDGF), transforming growth factor-b1 (TGF-b1), and vascular endothelial growth factor (VEGF). Furthermore, ProlozoneTM is especially effective for reduction pain. ProlozoneTM therapy can be used to address a variety of conditions including, arthritis, osteoarthritis, chronic joint pain, joint instability, spine pain, frozen shoulder and rotator cuff injuries, golfer’s elbow, tennis elbow, degenerative disc disease and others.

Dr. Wilson was trained and certified in Ozone/Prolozone Therapy by Frank Shallenberger, MD in 2012 and has been using it since, to treat a wide range of health conditions.