Ozone Therapy for Infections

How to administer ozone
Table of Contents

At a glance:

  1. Ozone therapy can help with various infections, including stubborn ones that tend not to respond or recur with conventional treatments.
  2. Ozone at therapeutic doses is not a drug but a biological response modifier. It modifies your immune and antioxidant defenses against infections, while stimulating healing responses.
  3. Although ozone kills microbes on contact, in the human body, it tends to work through lipid peroxidation byproducts and activates the immune system. In addition, at low doses, ozone therapy activates your antioxidant defenses and helps your body achieve balance so that the immune system can fully function. Boosting blood and tissue oxygenation, along with mitochondrial function also has antimicrobial and healing effects. 
  4. You can choose the most applicable route of ozone therapy for the location of your infections. For example, use rectal insufflation for gut, ear insufflation for ear and sinus, ozone bagging for skin, and vaginal insufflation for the female reproductive tract. However, most of these modalities also have systemic effects as lipid peroxidation products can get absorbed into the bloodstream.
  5. Ozone therapy may help overcome drug-resistant microbes as it has non-specific effects and breaks biofilms. Some studies also suggest that ozone therapy may help improve beneficial flora instead of killing all bacteria.
  6. To get started, download our ozone therapy guide here.

Ozone therapy is best known for its ability to help with infections, largely due to its unique ability to modulate and rejuvenate stagnant immune functions. The clinical literature has reported how it can turn around difficult-to-treat or even dire cases.

This therapy's effectiveness stems from its multifaceted biological impacts. Ozone itself is an antimicrobial and biofilm breaker. At the same time, oxygen-ozone therapy can stimulate the healing processes. Ozone can treat infection on its own or work alongside antimicrobials without creating antimicrobial resistance. 

In this article, we’ll cover the latest evidence and protocols for ozone therapy to treat various types of infections.

How Does Ozone Therapy Help with Infections?

  1. By direct antimicrobial effects

Ozone possesses direct antimicrobial properties on contact against [1]:

  • Bacteria by disrupting bacterial cell walls
  • Viruses by oxidizing protein and lipid coats
  • Fungi by compromising their cellular integrity 

These direct actions complement the immune system’s efforts in eradicating infections, making ozone therapy an effective add-on treatment to antimicrobial therapies.

During ozone therapy where ozone or ozonated oil or water is applied to your body, ozone therapy works a little differently than just ozone meeting microbes. Ozone typically reacts with various components in your tissues, creating lipid peroxidation byproducts (LOPs) and peroxides. These LOPs and peroxides have some antimicrobial effects and also activate the immune system. 

  1. Activation of immune cells

Ozone therapy can stimulate the production and function of key immune cells, so the body can better fight off pathogens. This may reduce the duration and severity of various bacterial, viral, and fungal infections [2].

3) Modulation of cytokine production

Ozone is not a drug, but a modifier of biological response. Ozone therapy can modulate cytokines, which are proteins that regulate immune response and blood cell production [3].

By modulation, we mean that the effect can be pro or anti-inflammatory based on what your body needs. It can also mitigate unhelpful or dangerous overreactions of the immune system, such as cytokine storm and sepsis.

4) Enhancement of antioxidant defense and redox balance

Oxidative stress can be either good or bad, depending on the context. For example, the immune system relies on oxidative species to communicate with one another, so oxidative stress can increase inflammation. However, immune responses to infections also create oxidative stress. Overall, excessive oxidative stress can cause more damage and inhibit effective immune responses.  

Ozone therapy induces therapeutic (small) doses of oxidative stress, which stimulates the body’s antioxidant defense mechanisms, including: 

  • Activating Nrf2, which increases the production of numerous antioxidant enzymes, such as superoxide dismutase and catalase [4, 5]. Nrf2 activation also increases the production of phase 2 detoxification enzymes and heat shock proteins that assist with protein folding.
  • Stimulating the synthesis of glutathione, which acts as a direct free radical scavenger crucial in the detoxification processes of the liver. 
  • Reducing the markers of oxidative damage in lipids, proteins, and DNA. 

By shifting the cellular redox state (oxidative stress levels), ozone therapy may also inhibit viral entry and replication [6]. 

5) Improving tissue oxygenation

Low oxygen can inhibit healing, and allow for infections and related complications. Ozone-oxygen therapy improves tissue oxygenation. According to a 1986 JAMA report, increased oxygenation can inhibit bacterial growth almost as much as antibiotics, especially when tissues start to die due to infections or lack of blood flow (infectious necrosis) [7]. 

This is how hyperbaric oxygen therapy can also help with infections [8]. However, hyperbaric therapy is less beneficial when the tissue doesn’t have enough new blood vessels built or when there is tissue death [9]. Whereas, ozone-oxygen therapy can deliver some benefits even without new blood vessels and with some tissue death [10]. 

6) Improving mitochondrial function and perhaps helping cell danger response

Your mitochondria (the cell’s main energy producers) are also responsible for sensing danger like infections and coordinating the response called the Cell Danger Response (CDR). During the CDR, the mitochondria are in a low metabolism state and emit low-grade inflammation signals. CDR is a defense state that protects most of the cells and body until the threat passes. However, ongoing CDR also means healing doesn’t occur [11]. 

Ozone has paradoxical effects. At low doses, it may improve mitochondrial function by improving oxygenation and activating antioxidant responses. At higher doses, it can be an oxidant that destroys the mitochondria. Therefore, selecting the right dose is crucial to getting the desired benefits.

A case report examined 6 patients receiving 10 pass high-dose ozone therapy. They found a significant increase in mitochondrial activity and health in peripheral blood mononuclear cells after 2 sessions in a week [12]. 

This is one of the reasons treatments that boost mitochondrial function seem to be beneficial for chronic low-grade inflammation. While there is no clinical evidence that confirms that ozone therapy helps with CDR, it’s a reasonable explanation as to why ozone therapy can powerfully resolve infections or other inflammatory conditions. 

Also, better oxygen utilization and mitochondrial function provide immune cells with enough energy to function, especially during demanding times like an infection [13].

7) Improving blood flow

Ozone may improve circulation in various ways, including:

  • Creating ozonides that enhance the flexibility of red blood cells. This allows them to pass more easily through small capillaries, delivering oxygen more effectively to tissues [14, 15].
  • Stimulating cells that line the blood vessels to produce nitric oxide (NO), which relaxes vascular smooth muscle, leading to the dilation of blood vessels. This dilation increases blood flow, which improves oxygen delivery and the removal of metabolic waste and carbon dioxide. 
  • Ozone inhibits several clotting factors–it reduces platelet aggregation and lowers fibrin [16]. However, IV ozone therapies tend to also involve adding heparin to prevent blood clots.

These are particularly beneficial in ischemic conditions, where blood supply is compromised, such as peripheral artery disease and diabetic ulcers. 

How Various Types of Ozone Therapy Affect the Local and Systemic Immune Functions

Click here to download our ozone therapy guide

Ozone autohemotherapy (AHT) and high-dose IV ozone treatment

Autohemotherapy is the most studied form of ozone therapy. It involves withdrawing a small amount of blood, 10 - 20 cc for minor and 100 - 300 cc for major autohemotherapy, then mixing it with ozone-oxygen gas before reintroducing it back to the body. 

This gas exposure allows ozone to react with the blood components, creating ozonides, reactive oxygen species, and lipid peroxides. It also improves blood oxygenation as over 95% of the gas mix is oxygen. These activate the immune system and stimulate the body’s antioxidant defense [17].

Autohemotherapy may help treat or prevent infections, such as [18–21]:

  • Sacroiliitis 
  • Viral infectionssome text
    • Hepatitis B
    • Hepatitis C
    • Cold or upper respiratory tract infections and pneumonia
    • Herpes and herpes zoster [22]
    • (Minor) Epstein Barr virus-related hives [23]
  • Osteonecrosis [21]
  • Lyme disease [24]
  • Tick bite cellulitis (high dose)

A clinical case study tracked the treatment of a 39-year-old man suffering from lower back pain and stiffness due to sacroiliitis, an inflammation of the hip bones. The patient had severe motion limitation in his lumbar regions, a pain score of 7 on a visual analog scale (VAS), and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3. Diagnostic tests showed active inflammation on MRI, elevated erythrocyte sedimentation rate, and positive HLA-B27 antigen, an inflammatory marker.

The patient received oxygen-ozone autohemotherapy three times a week for two months. Treatment showed a significant decrease in pain (VAS score reduced to 1.0) and disease activity (BASDAI score reduced to 1.4). MRI scans six months after treatment showed no swelling, indicating no active inflammation.

The case highlights the potential of oxygen-ozone therapy as a minimally invasive and effective treatment for inflammatory conditions. However, further studies are necessary to confirm these findings and establish standardized protocols for broader clinical applications.

Extracorporeal blood oxygenation-ozonation (EBOO) 

Extracorporeal blood oxygenation-ozonation (EBOO) refers to the biggest IV ozone therapy where 1.5 - 7 liters of blood is removed from the body and infused with ozone-oxygen gas before returning the blood into the body with another vein. It delivers the most ozone of all kinds of IV ozone therapy – up to 460,000 micrograms in an hour.

EBOO is indicated in severe and perhaps life-threatening conditions where most other therapies fail, including:

  • Sepsis [26]
  • Ischemic limb disease
  • Peripheral arterial disease [10]
  • Hepatitis
  • Lipodystrophies 
  • Severe viral or bacterial infections
  • Prolonged symptoms after infections 
  • Necrotizing fasciitis (flesh-eating bacteria)

Ozone ear insufflation or auricular ozone therapy

Ozone ear insufflation involves administering ozone-oxygen gas into the ear canal. It’s typically used for conditions affecting the ears, head, jaws, and upper respiratory tract. 

When ozone gas enters the ear canal, it can come into direct contact with pathogens (bacteria, viruses, fungi). Ozone's oxidizing properties can disrupt the cell walls of bacteria and the envelopes of viruses, inactivating these microbes [25]. Ozone can also break biofilms, exposing the microbes to ozone or other antimicrobials that might be used concurrently. 

At the same time, the ozone can stimulate local healing processes and immune responses. These effects might explain why ozone can help resolve stubborn ear, nose, and throat conditions.

Although primarily a local treatment, small amounts of ozone or its reactive byproducts might be absorbed into the bloodstream through the dense blood vessels of the ear canal and middle ear. This could potentially stimulate immune response throughout the body.

Ozone ear insufflation may lead to improvements in a variety of infections, including [27–30]:

  • Sinus infections
  • Ear discharge and infections
  • Eardrum inflammation (meso tympanitis)
  • Cold (caused by numerous viruses, most commonly the rhinovirus family)
  • Flu (caused by the influenza virus family)

Click here to download our ozone therapy guide

Rectal insufflation

Ozone rectal insufflation is a method of administering ozone gas into the gut through the rectum.  It is less invasive and may be more easily tolerated than intravenous routes

This technique has both local (gut) and whole-body effects because the rectal mucosa has an extensive blood and lymph supply that can absorb ozonides and oxidation byproducts. Also, 70 - 80% of immune cells are in the gut, so it makes sense that rectal insufflation can have large effects on the immune system [31].

Rectal insufflation can help with:

  • Pathogens in the lower gastrointestinal tract 
  • Local infections in the lower intestine or rectum 
  • Improving the gut flora, which affects overall health [32]
  • Gut lining and intestinal cell health (according to a mouse model) [33]
  • Activating immune cells and the production of cytokines and other immune mediators, both in the gut and throughout the body
  • Infections and inflammation elsewhere in the body (due to systemic effects)

There are published reports of rectal insufflation improving even ear disorders, respiratory conditions, and diabetes.

A randomized clinical trial examined 101 patients with type 2 diabetes and diabetic foot ulcers. The ozone group (52 participants) received ozone therapy through local (on the foot lesion) and rectal insufflation, while the control group (49 participants) was treated with standard of care including topical and systemic antibiotics.

Over 20 days, patients treated with ozone showed improved blood sugar control compared to the baseline and the antibiotic-treated group. Ozone therapy mitigated oxidative stress by decreasing levels of organic peroxides and activating superoxide dismutase. Indicators of blood vessel damage improved significantly in the ozone group. Also, the ozone group exhibited better healing of foot lesions leading to fewer amputations (3 out of 52) than in the antibiotic group (7 out of 49).

The study demonstrates that ozone therapy could be a potent alternative to antibiotic therapy for managing diabetes and related foot ulcers. These findings suggest that ozone therapy not only helps in controlling blood sugar levels but also reduces oxidative stress and improves wound healing in diabetic patients [34].

Click here to download our ozone therapy guide

Breathing ozone oil

Breathing ozonated oil, often referred to as ozonated oil inhalation or nebulization, involves breathing ozone bubbled through plant-based culinary oil.

This form of therapy makes it possible to deliver the antimicrobial and balancing effects of ozone therapy to the lungs, without the harm of inhaling ozone. 

The ozone treatment group showed:

  • A statistically significant reduction in the length of hospital stay
  • Reduction in C-reactive protein levels (an inflammatory marker)
  • Significantly reduced viral load
  • Better CT lung scores compared to the control group

No statistically significant differences were found between the two groups in terms of D-dimer, urea, lactate dehydrogenase, lymphocyte, leukocyte, and platelet counts – other markers of inflammation and immune response.

Compared to the control group, ozone oil inhalation for lung disinfection during respiratory illness can help with [35]:

  • Significantly reducing the rate of pneumonia
  • Expediting response to medical treatment
  • Reducing viral loads

Vaginal insufflation

Ozone vaginal insufflation involves the introduction of ozone gas into the vaginal cavity. It can help treat local infections and inflammatory conditions in the female reproductive tract. It may also have some systemic effects

There is very limited quality evidence available for vaginal insufflation. The available literature often includes case studies or anecdotal reports rather than controlled clinical trials.

Vaginal insufflation may help with bacterial, fungal, or viral infections of the female reproductive tract, especially stubborn cases, such as:

  • Vulvovaginitis or colpitis from candida or other infections [36]
  • Vaginosis
  • Cervical infections
  • Papillomavirus
  • Endometritis
  • Interstitial cystitis from infections or other causes

A randomized controlled trial enrolled 50 women with recurrent candidal vulvovaginitis. Twenty-five received the standard of care which was a topical and systemic antifungal (150 mg fluconazole every 3 days for 3 doses). The ozone group received vaginal ozone insufflation, which was 6 minutes of 50 mL/min, 20 - 40 microgram ozone/mL every other day for 12 sessions. The partners of both groups also received a single dose of 150 mg of fluconazole. After the treatments were completed, 22 patients in the ozone group achieved clinical cure, compared to 14 in the standard treatment group. Out of the cured patients, 1 out of 22 in the ozone group had recurring infection, whereas 5 out of the14 cured by standard treatment recurred within 2 - 4 weeks after treatments ended. The authors concluded that ozone vaginal insufflations were more effective than the antifungals [37].

Topical ozone oils and oil-pulling

Ozone oil can be applied topically on the skin or in the mouth, with antimicrobial effects [39]. The ozonated oil delivers ozonides and peroxides on the skin, which can disrupt the membranes of microbes and modulate the skin's immune system. Ozone oil can also break biofilms and stimulate tissue regeneration, so ozone oil pulling can help stubborn dental conditions that involve bacteria.

Ozone oil on the skin may help treat skin infections such as [39]:

  • Methicillin-resistant Staphylococcus aureus (MRSA)-infected ulcer (animal model) [40]
  • Tinea capitis (fungal infection of the scalp)
  • Herpes zoster
  • Skin ulcer [41]
  • Diabetic foot ulcers, including removing MRSA biofilms from diabetic foot ulcers [42]
  • Skin and leg ulcers
  • Fungal infections
  • Common warts

A randomized controlled trial examined the effect of incorporating ozonated olive oil-based mouthwash into non-surgical periodontal therapy for 96 patients with periodontitis. Participants were divided into two groups. The study group received scaling and root planing (SRP) combined with an ozonated olive oil-based mouthwash, while the control group received only SRP.

After 3 months, significant improvements were observed in plaque index (PI), bleeding on probing (BoP), probing pocket depth (PPD), and salivary MMP-8 levels in both groups throughout the study. The addition of ozonated olive oil mouthwash to SRP was more effective in reducing salivary MMP-8 levels compared to SRP alone. 

These findings suggest that integrating ozonated oil mouthwash with standard non-surgical periodontal therapy could be a more effective strategy for reducing periodontal inflammation and tissue damage in patients with periodontitis [43].

Ingesting ozone oils or water

Ingesting ozonated oils or ozone water is a practice in which individuals consume water or oils that have been infused with ozone gas. This method is purported to harness the antimicrobial and immune-modulating properties of ozone, aiming to benefit both local oral, gastrointestinal, and systemic health.

There are not many clinical studies on ingested ozone oil or water. These do not replace systemic therapies like ozone IV. However, they may have antimicrobial effects in the stomach or upper intestine, such as:

  • Helping with stomach ulcers, due to ozone’s wound-healing effect
  • Slowing the growth of parasites, including amoebic ones like giardia [44]

How does ingested ozone oil affect the gut cells? There is a test tube study that examined this.

An in vitro study investigated the anti-inflammatory effects of Ozoile®, a stable ozonide from olive oil, on human colonic (HT-29) and monocytic (THP-1) cells, exploring its potential for treating intestinal inflammation.

HT-29 and THP-1 cells were stimulated with lipopolysaccharide (LPS, a component of bacteria cell wall) to induce inflammation, both with and without Ozoile®. The study assessed biomarkers of inflammation, tight junction proteins, and the adhesion molecule ICAM.

In HT-29 cells, Ozoile® effectively inhibited the LPS-induced inflammation, enzymes that cause leaky gut (NOS2, MMP-2), and altered the expression of tight junction proteins (ZO-1, CLDN1). This means Ozoile® strengthened the gut barrier despite the inflammation source. Additionally, it enhanced the expression of antioxidant proteins Nrf2 and SOD2.

In THP-1 cells, Ozoile® treatment also counteracted the inflammation from LPS. 

Given the promising in vitro results, ozone oil ingestion might be useful for gut healing programs or even some gut inflammation conditions [45]. 

Ozone saunas and topical exposure to ozone gas

Ozone saunas are a form of therapy that combines the benefits of sauna heat and ozone gas. The user sits in an enclosed space where heat, steam, and ozone are introduced, purportedly to detoxify the body, enhance skin health, and stimulate immune functions. 

The heat from the sauna increases pore opening and sweating, which may facilitate the absorption of ozonides and lipid peroxides into the body. Both ozone-oxygen and heat also have some effects on the immune system.

Ozone bagging, on the other hand, involves surrounding a body part such as a foot with ozone-oxygen gas in a bag.

In a systematic review, skin exposure to ozone gas, such as from bagging and sauna has some benefits against infectious skin conditions including [46]:

  • Acne
  • Diabetic foot ulcer
  • Wound healing
  • Skin ulcer

An animal study also reported a potential beneficial effect on toenail fungus, a typically stubborn condition [47]

Ozone water wash (hydrotherapy)

Ozone water is useful as a disinfectant, such as on wounds and during dental procedures [48]. Ozonated hydrotherapy is a therapeutic practice that involves dissolving ozone gas in water and using the ozone water to wash the treated body parts [5]. This treatment modality is particularly effective in managing a range of dermatological conditions, including:

  • Infectious skin diseases
  • Atopic dermatitis
  • Psoriasis
  • Pemphigus
  • Diabetic foot ulcers
  • Vaginal or cervical conditions

It is also utilized to cleanse burns and scald wounds, expedite wound healing, and enhance skin repair following laser cosmetology procedures.

Ozonated water reduces inflammation, promoting microbial clearance and accelerating tissue regeneration. 

Depending on the specific skin lesions, different application methods such as debridement, soaking, or wet compression can be employed, making the therapy adaptable to a wide range of clinical scenarios.

Some limitations include:

  • Instability of ozone: Ozone is unstable in water, with a half-life of only 27 minutes at 20°C, which limits the storage and transportation of ozonated water.
  • Operational requirements: Due to the precise control needed over ozone concentration, water temperature, and treatment duration, ozoehydrotherapy requires administration by trained healthcare professionals.

Ozonated hydrotherapy offers a simple, flexible, and age-inclusive option for managing and treating various skin conditions and wounds. 

Its effectiveness, however, is contingent upon proper application techniques and careful monitoring of treatment parameters to ensure safety and efficacy. Further research and development could potentially expand its applicability and ease of use in clinical settings.

A systematic review and meta-analysis evaluated all (a total of 390, 5 of which involved water or saline) clinical studies that tested the effects of ozonated liquid (water or oil) treatment on epithelial wounds. They concluded that these liquids may shorten wound healing by about a week. All studies show that it enhanced wound healing [49].

Aside from treating or preventing infections, ozone water doesn’t seem to disrupt the microbial flora of the area it’s exposed to. 

A prospective, non-controlled clinical trial evaluated the impact of ozonated water lavage on vaginal microecology in 30 female volunteers without vaginal infection. Ozone lavage was performed for 5 minutes/day followed by a vaginal swab for three consecutive non-menstrual days. 

There were no significant changes in microbial density, diversity, or dominant flora (correlation coefficient <0.2), suggesting that ozonated water does not disrupt the balance of these beneficial bacteria. The findings suggest that ozonated water lavage could be a safe method for treating vaginitis with minimal impact on the natural and beneficial vaginal flora, although vaginitis was not directly researched. This method maintains the dominance of Lactobacillus, crucial for vaginal health, while potentially reducing pathogenic bacteria [50].

Click here to download our ozone therapy guide

How Does Ozone Help Various Types of Infections 

Viral infections

Ozone therapy can both deactivate viruses and stimulate the right immune response. For example, ozone therapy could be effective in [19, 22, 51]:

  • Respiratory infections like colds and flu
  • Herpes zoster (shingles)
  • Hepatitis B
  • Hepatitis C
  • Coronavirus

However, ozone therapy is not effective for HIV, according to a clinical trial published by Dr. Bocci [52].

An observational study of 223 patients explored the efficacy and safety of ozone/oxygen gas therapy in treating liver fibrosis in patients with chronic hepatitis C. Participants received an ozone/oxygen gas mixture for 12 weeks. Liver biopsies were performed after the treatment period to assess changes in liver fibrosis and inflammation.

Ozone treatment resulted in a statistically significant decrease in the mean stage of fibrosis, from 1.98 to 1.41, and in the mean grade of inflammation, from 10.08 to 7.94 (p < 0.001). Treatment also resulted in decreased viral load. The significant reductions in stages of fibrosis and grades of inflammation demonstrate the therapy’s potential for managing liver conditions associated with chronic viral infections [53].

Bacterial infections

Ozone therapy is increasingly recognized for its potential in treating bacterial infections, particularly given its unique mechanisms that differ significantly from those of traditional antibiotics. 

Its ability to stimulate immune responses, directly kill bacteria, and induce biochemical changes that hinder bacterial survival offers a broad range of therapeutic benefits. Ozone can specifically help fight [54–57]:

  • Cariogenic bacteria that cause tooth decay
  • MRSA
  • Staphylococcus aureus
  • Streptococcus mutans, which causes tooth decay, blood infections, and heart inflammation
  • Klebsiella pneumoniae

A randomized controlled trial examined 48 people diagnosed with deep carious lesions. They received gaseous ozone or 2% chlorhexidine after pulp removal.

Both ozone and chlorhexidine significantly reduced the number of total bacteria in treated carious lesions. In the ozone-treated group, blood vessel growth factors (VEGF) and nitric oxide synthase (nNOS) levels in dental pulp were significantly higher (VEGF: p < 0.001, nNOS: p = 0.012) compared to the control group, while SOD activity was lower (p = 0.001).

The impact of ozone on pulp biomarkers such as VEGF, nNOS, and SOD suggests that ozone not only effectively disinfects but also demonstrates biocompatibility with dental pulp tissue [58].

Parasitic infections

Ozone therapy may help with parasitic infections, since its unique oxidative properties may overcome resistance to conventional antiparasitic drugs. 

Ozone is a strong oxidant that can damage the cell structures of parasites through oxidation. This includes disruption of the cell membrane integrity, oxidation of critical proteins, and damage to the parasites’ reproductive and metabolic functions.

This direct action can reduce the parasite load rapidly and effectively, potentially treating the infection without the need for traditional antiparasitic drugs.

Ozone induces a controlled oxidative stress that stimulates the body’s antioxidant defenses. This can lead to the production of reactive oxygen species (ROS) and lipid oxidation products (LOPs), like 4-hydroxynonenal (HNE), which have additional antimicrobial and immunomodulatory effects. These oxidative mediators can directly inhibit parasite growth and influence immune pathways that help in clearing infections.

While the use of ozone therapy for parasitic infections is supported by various plant and water studies showing its effectiveness against parasites, comprehensive human clinical trials are less common [59]. 

Unlike broad-spectrum antiparasitic drugs, which can disrupt the gut microbiota and lead to intestinal upset, ozone therapy is more selective in its antimicrobial effects, potentially preserving beneficial bacteria while targeting parasites.

Fungal infections

Ozone therapy presents a promising alternative or adjunct to conventional antifungal treatments, especially when the fungal infections are resistant to antifungals. Also, fungi tend to be opportunistic organisms that infect weak hosts, so ozone’s immune-modulating effects may be especially beneficial.  

Ozone's unique mechanisms of action, including its direct fungicidal effects and immune modulation capabilities, offer a comprehensive approach that could address the limitations of current antifungal therapies.

Fungal species that ozone may be effective at fighting include [47]:

  • Candida albicans - causes oral thrush
  • Acremonium chrysogenum - causes mycotema, a chronic, destructive infectious disease of the subcutaneous tissues
  • Aspergillus terreus - causes numerous lung infections
  • Epidermophyton floccosum - causes ringworm, jock itch, and nail infections
  • Fusarium solani - causes skin and nail infections
  • Microsporum canis - causes ringworm and alopecia
  • Trichophyton mentagrophytes - causes ringworm
  • Trichophyton rubrum - causes athlete’s foot, jock itch, and ringworm

In a randomized controlled trial, 40 patients with oral candidiasis were randomly assigned to receive either topical ozone therapy or topical clotrimazole. The treatments were administered to assess their effectiveness in reducing salivary Candidal CFU counts.

Both treatments resulted in a gradual but significant reduction in Candidal CFU counts. By the end of the treatment period, the reduction in CFU counts was more pronounced in the ozone group (60.5% reduction) compared to the clotrimazole group (32.3% reduction).

In the ozone group, 70% of patients saw a reduction in candidiasis to the point of becoming carriers (reduction from 14 to 6 patients), whereas, in the clotrimazole group, the reduction was from 13 patients (65%) to 8 patients (40%). 

These findings suggest that ozonated water could be a valuable and effective alternative to conventional antifungal treatments for oral candidiasis, offering a non-pharmacological option that aligns with the broader use of ozone therapy in dental and medical fields [60]. 

An in vitro/ex-vivo pig study explored the development of a rapid treatment method for onychomycosis, a fungal nail infection. The method consisted of combining dual-diode lasers with wavelengths of 405 nm and 639 nm and ozone therapy up to 80 ppm against various fungal strains.

In the test tube, fungal strains were grown on PDA agar medium. Ex vivo, pig’s hooves samples were used. In vitro, at an ozone concentration of 40 ppm, all tested fungal species were inhibited except for S. brevicaulis, which showed no inhibition compared to ozone treatment alone. 

On the removed pig toenail, complete inhibition was observed in A. chrysogenum and E. floccosum. T. mentagrophytes and T. rubrum exhibited 75% growth inhibition. M. canis demonstrated a delay in sporulation. S. brevicaulis and A. terreus did not exhibit any growth inhibition under the tested conditions.

The combination of laser and ozone treatments showed significant potential in rapidly reducing fungal growth in models of onychomycosis, suggesting this method could be a viable and faster alternative to traditional antifungal medications, which often come with side effects and require lengthy treatment periods [48].

Closing Remarks

Ozone therapy, whether applied as a gas, in water, or as an ozonated oil, offers significant benefits, ranging from reducing infection loads to enhancing tissue repair and modulating immune responses. Particularly noteworthy is its efficacy in treating stubborn conditions like oral candidiasis, chronic hepatitis C, and skin or mouth ulcers, periodontitis where traditional treatments either fall short or lead to adverse side effects.

Ozone’s ability to act as an antimicrobial, anti-inflammatory, and immunostimulating agent highlights its role in addressing complex clinical challenges, especially in cases where antibiotic resistance or the side effects of conventional drugs complicate treatment. Keep in mind that the evidence is still very limited. Often, it’s possible and beneficial to combine both ozone and standard of care. Most importantly, always consult your doctor when it comes to treating, preventing, or managing infections.

References

Xue, W., Macleod, J. and Blaxland, J. (2023) The Use of Ozone Technology to Control Microorganism Growth, Enhance Food Safety and Extend Shelf Life: A Promising Food Decontamination Technology. Foods 12 https://doi.org/10.3390/foods12040814

Weismann, D. and Binder, C. J. (2012) The innate immune response to products of phospholipid peroxidation. Biochim. Biophys. Acta 1818, 2465–2475

de Sire, A., Marotta, N., Ferrillo, M., Agostini, F., Sconza, C., Lippi, L., et al. (2022) Oxygen-Ozone Therapy for Reducing Pro-Inflammatory Cytokines Serum Levels in Musculoskeletal and Temporomandibular Disorders: A Comprehensive Review. Int. J. Mol. Sci. 23 https://doi.org/10.3390/ijms23052528

Galiè, M., Covi, V., Tabaracci, G. and Malatesta, M. (2019) The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure. Int. J. Mol. Sci. 20 https://doi.org/10.3390/ijms20164009

Liu, L., Zeng, L., Gao, L., Zeng, J. and Lu, J. (2023) Ozone therapy for skin diseases: Cellular and molecular mechanisms. Int. Wound J. 20, 2376–2385

Checconi, P., De Angelis, M., Marcocci, M. E., Fraternale, A., Magnani, M., Palamara, A. T., et al. (2020) Redox-Modulating Agents in the Treatment of Viral Infections. Int. J. Mol. Sci. 21 https://doi.org/10.3390/ijms21114084

Knighton, D. R., Halliday, B. and Hunt, T. K. (1986) Oxygen as an antibiotic. A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearanceArch. Surg. 121, 191–195

Memar, M. Y., Yekani, M., Alizadeh, N. and Baghi, H. B. (2019) Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections. Biomed. Pharmacother. 109, 440–447

McCurdy, B. (2017) Can HBOT Heal Ischemic Wounds? Podiatry Today 30

10  Di Paolo, N., Bocci, V., Salvo, D. P., Palasciano, G., Biagioli, M., Meini, S., et al. (2005) Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease. Int. J. Artif. Organs 28, 1039–1050

11  Naviaux, R. K. (2014) Metabolic features of the cell danger response. Mitochondrion 16, 7–17

12  König, B. and Lahodny, J. (2022) Ozone high dose therapy (OHT) improves mitochondrial bioenergetics in peripheral blood mononuclear cells. Transl Med Commun 7, 17

13  Shore, S. A. (2019) The Metabolic Response to Ozone. Front. Immunol. 10, 2890

14  Xiao, W., Tang, H., Wu, M., Liao, Y., Li, K., Li, L., et al. (2017) Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway. Biosci. Rep. 37 https://doi.org/10.1042/BSR20170658

15  Ebensberger, U., Pohl, Y. and Filippi, A. (2002) PCNA-expression of cementoblasts and fibroblasts on the root surface after extraoral rinsing for decontamination. Dent. Traumatol. 18, 262–266

16  Maslennikov, O. V., Sharov, I. G., Potekhina, I. P., Dushkina, N. G., Kryzhanovskaia, N. A., Maslennikova, N. O., et al. (1997) [Effect of ozone therapy on hemostatic changes in patients with vascular atherosclerosis]Klin. Med.  75, 35–37

17  Elvis, A. M. and Ekta, J. S. (2011) Ozone therapy: A clinical review. J. Nat. Sci. Biol. Med. 2, 66–70

18  Moreno-Fernández, A., Macías-García, L., Valverde-Moreno, R., Ortiz, T., Fernández-Rodríguez, A., Moliní-Estrada, A., et al. (2019) Autohemotherapy with ozone as a possible effective treatment for Fibromyalgia. Acta Reumatol. Port. 44, 244–249

19  Niño-Sandoval, T. C., Rocha, N. S., Sarinho, F. W., Vasconcelos, C. F. de M., Vasconcelos, A. F. de M. and Vasconcelos, B. C. (2021) Effect of autohemotherapy in the treatment of viral infections - a systematic review. Public Health 201, 78–88

20  Biedunkiewicz, B., Tylicki, L., Nieweglowski, T., Burakowski, S. and Rutkowski, B. (2004) Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study. Int. J. Artif. Organs 27, 29–34

21  An, J.-X., Wu, G.-P., Niu, K., Wei, Y.-P., Liu, H., Gao, X.-Y., et al. (2022) Treatment of Femoral Head Osteonecrosis with Ozone Therapy: Pilot Trial of a New Therapeutic Approach. Pain Physician 25, E43–E54

22  Yang, J., Luo, K., Chen, Z.-J., Zhang, G.-H., Yao, X., Feng, S.-X., et al. (2023) Clinical efficacy and metabolomic analysis of ozone major autohemotherapy for the treatment of herpes zoster. Postepy Dermatol Alergol 40, 693–698

23  Manfredi, G. and Apuzzo, D. (2020) Successful Ozone Treatment of EBV and HSV-Related Viral Urticaria. Frontiers in Medical Case Reports, Frontiers in Medical Case Reports 1, 1–6

24  Çarli, A. B. and Incedayi, M. (2017) Oxygen-ozone autohemotherapy in sacroiliitis. Acta Reumatol. Port. 42, 334–335

25  Skorup, P., Fransson, A., Gustavsson, J., Sjöholm, J., Rundgren, H., Özenci, V., et al. (2022) Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis. Intensive Care Med Exp 10, 14

26  Peng, T.-R., Cheng, H.-Y., Wu, T.-W. and Ng, B.-K. (2022) Effectiveness of Oil Pulling for Improving Oral Health: A Meta-Analysis. Healthcare (Basel) 10 https://doi.org/10.3390/healthcare10101991

27  Petrov, G. M., Kudriavtsev, B. P. and Akulich, I. I. (1996) [The efficacy of using ozone preparations in the combined treatment of paranasal sinusitis]Voen. Med. Zh. 317, 26–8, 80

28  Shakov, V. I. and Edeleva, A. N. (1999) [Reasons for the application of medical ozone in the treatment of chronic purulent mesotympanitis]Vestn. Otorinolaringol. 48–49

29  Hernández Rosales, F. A., Calunga Fernández, J. L., Turrent Figueras, J., Menéndez Cepero, S. and Montenegro Perdomo, A. (2005) Ozone therapy effects on biomarkers and lung function in asthma. Arch. Med. Res. 36, 549–554

30  Dubuis, M.-E., Racine, É., Vyskocil, J. M., Turgeon, N., Tremblay, C., Mukawera, E., et al. (2021) Ozone inactivation of airborne influenza and lack of resistance of respiratory syncytial virus to aerosolization and sampling processes. PLoS One 16, e0253022

31  Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J. and Knippels, L. M. J. (2021) The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients 13 https://doi.org/10.3390/nu13030886

32  Mallaeva, R. M. (2018) The effect of ozone therapy on the state of the intestinal microbiota

33  Sukhotnik, I., Starikov, A., Coran, A. G., Pollak, Y., Sohotnik, R. and Shaoul, R. (2015) Effect of ozone on intestinal epithelial homeostasis in a rat model. Rambam Maimonides Med J 6, e0006

34  Martínez-Sánchez, G., Al-Dalain, S. M., Menéndez, S., Re, L., Giuliani, A., Candelario-Jalil, E., et al. (2005) Therapeutic efficacy of ozone in patients with diabetic foot. Eur. J. Pharmacol. 523, 151–161

35  Dengiz, E., Özcan, Ç., Güven, Y. İ., Uçar, S., Ener, B. K., Sözen, S., et al. (2022) Ozone gas applied through nebulization as adjuvant treatment for lung respiratory diseases due to COVID-19 infections: a prospective randomized trial. Med. Gas Res. 12, 55–59

36  Tapia, A. (2015) Ozone therapy in the treatment of recurrent vulvo-vaginitis by Candida albicans

37  Khairy, H., Ibrahim, M., Abdul Hadi, R. and El-Taweel, H. (2020) Vaginal ozone insufflation in the treatment of recurrent candidal vulvovaginitis: Randomized control trial. Evid. Based Women S Health J., Egypts Presidential Specialized Council for Education and Scientific Research 0, 0–0

38  Radzimierska-Kaźmierczak, M., Śmigielski, K., Sikora, M., Nowak, A., Plucińska, A., Kunicka-Styczyńska, A., et al. (2021) Olive Oil with Ozone-Modified Properties and Its Application. Molecules 26 https://doi.org/10.3390/molecules26113074

39  Machado, A. U. and Contri, R. V. (2022) Effectiveness and Safety of Ozone Therapy for Dermatological Disorders: A Literature Review of Clinical Trials. Indian J. Dermatol. 67, 479

40  Silva, V., Peirone, C., Capita, R., Alonso-Calleja, C., Marques-Magallanes, J. A., Pires, I., et al. (2021) Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer. Biology  10 https://doi.org/10.3390/biology10050372

41  Anzolin, A. P., da Silveira-Kaross, N. L. and Bertol, C. D. (2020) Ozonated oil in wound healing: what has already been proven? Med. Gas Res. 10, 54–59

42  Silva, V., Peirone, C., Amaral, J. S., Capita, R., Alonso-Calleja, C., Marques-Magallanes, J. A., et al. (2020) High Efficacy of Ozonated Oils on the Removal of Biofilms Produced by Methicillin-Resistant Staphylococcus aureus (MRSA) from Infected Diabetic Foot Ulcers. Molecules 25 https://doi.org/10.3390/molecules25163601

43  Nardi, G. M., Cesarano, F., Papa, G., Chiavistelli, L., Ardan, R., Jedlinski, M., et al. (2020) Evaluation of Salivary Matrix Metalloproteinase (MMP-8) in Periodontal Patients Undergoing Non-Surgical Periodontal Therapy and Mouthwash Based on Ozonated Olive Oil: A Randomized Clinical Trial. Int. J. Environ. Res. Public Health 17 https://doi.org/10.3390/ijerph17186619

44  Bocci, V. Preparation of Ozonated Water and Oil for the Topical Therapy – Ozone as a Drinking Water Disinfectant: Ozone Disinfection to Prevent Nosocomial Infections. Ozone: Sci. Eng., Nature Publishing Group 9

45  Bertuccio, M. P., Rizzo, V., Arena, S., Trainito, A., Montalto, A. S., Caccamo, D., et al. (2023) Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes. Curr. Issues Mol. Biol. 45, 1333–1348

46  Oliveira Modena, D. A., de Castro Ferreira, R., Froes, P. M. and Rocha, K. C. (2022) Ozone Therapy for Dermatological Conditions: A Systematic Review. J. Clin. Aesthet. Dermatol. 15, 65–73

47  Fernández, J., Del Valle Fernández, I., Villar, C. J. and Lombó, F. (2021) Combined laser and ozone therapy for onychomycosis in an in vitro and ex vivo model. PLoS One 16, e0253979

48  Loncar, B., Mravak Stipetic, M., Matosevic, D. and Tarle, Z. (2009, February) Ozone application in dentistry. Arch. Med. Res.

49  Romary, D. J., Landsberger, S. A., Bradner, K. N., Ramirez, M. and Leon, B. R. (2023) Liquid ozone therapies for the treatment of epithelial wounds: A systematic review and meta-analysis. Int. Wound J. 20, 1235–1252

50  Zhang, Q.-Q., Zhang, L., Liu, Y., Wang, Y., Chen, R., Huang, Z.-Y., et al. (2019) Effect of ozonated water on normal vaginal microecology and Lactobacillus. Chin. Med. J.  132, 1125–1127

51  Aghamohammadi, D., Shakouri, S. K., Jahanpanah, N. and Dolatkhah, N. (2024) Effects of adjuvant ozone autohemotherapy combined with routine treatment on clinical and paraclinical features of mechanically ventilated COVID-19 patients in the intensive care unit: a pilot randomized controlled trial. Med. Gas Res. 14, 67–74

52  Bocci, V., Venturi, G., Catucci, M., Valensin, P. E. and Zazzi, M. (1998) Lack of efficacy of ozone therapy in HIV infection. Clin. Microbiol. Infect. 4, 667–669

53  Sadek, A., Abd El Hady, A. M., Olfat, H., Abd El Hady, A. A., Wafy, W., Zaki, M., et al. (2024) Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients. J. Complement. Integr. Med. 21, 131–138

54  Song, M., Zeng, Q., Xiang, Y., Gao, L., Huang, J., Huang, J., et al. (2018) The antibacterial effect of topical ozone on the treatment of MRSA skin infection. Mol. Med. Rep. 17, 2449–2455

55  Johansson, E., Claesson, R. and van Dijken, J. W. V. (2009) Antibacterial effect of ozone on cariogenic bacterial species. J. Dent. 37, 449–453

56  Sancakli, H. S., Siso, S. H., Yildiz, S. O. and Gökçe, Y. B. (2018) Antibacterial Effect of Surface Pretreatment Techniques against Streptococcus Mutans. Niger. J. Clin. Pract. 21, 170–175

57  Piletić, K., Kovač, B., Perčić, M., Žigon, J., Broznić, D., Karleuša, L., et al. (2022) Disinfecting Action of Gaseous Ozone on OXA-48-Producing Klebsiella pneumoniae Biofilm In Vitro. Int. J. Environ. Res. Public Health 19 https://doi.org/10.3390/ijerph19106177

58  Krunić, J., Stojanović, N., Đukić, L., Roganović, J., Popović, B., Simić, I., et al. (2019) Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removalClin. Oral Investig. 23, 785–792

59  Steel, A., Platz, M. S., Riglos, A.-J., Garcia, B. J., Jacob, J. and Jarvi, S. I. (2022) Larvicidal Efficacy of Ozone and Ultrasound on Angiostrongylus cantonensis (Rat Lungworm) Third-Stage Larvae. Foods 11 https://doi.org/10.3390/foods11070953

60  Khatri, I., Moger, G. and Kumar, N. A. (2015) Evaluation of effect of topical ozone therapy on salivary Candidal carriage in oral candidiasis. Indian J. Dent. Res. 26, 158–162

 

//new code to transform the table