Ozone saline IV drip

At a Glance:

• An ozone saline drip involves bubbling medical-grade 5 to 10 mcg/mL ozone-oxygen through approximately 200 mL of sterile 0.9% NaCl until saturation, followed by immediate IV drip.
• Ozone saline drip is a systemic oxidative therapy option that avoids the complexities and risk of blood handling associated with major autohemotherapy, since ozone saline drips use pre-saturated saline rather than withdrawn blood [1].
• When ozone reacts with chloride ions in saline, trace amounts of chlorite, chlorate, and perchlorate can form. This is a controversial point in the safety of ozone saline drip [1].
• The ozone saline drip became popular in busy Russian hospitals because it eliminates the need for blood withdrawal and reinfusion, making it a practical option for busy hospitals and situations where blood removal may be impractical. 
• Major proponents of ozone therapy, like Dr. Bocci and the World Federation of Ozone Therapy, consider ozone saline drip to be higher risk due to chlorite formation and of lower benefit than autohemotherapy due to lower ozone doses. 

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Ozone saline drip (O3SS) is a controversial ozone treatment. While easier to administer and avoiding difficulties related to blood removal and handling, saline ozonation runs the risk of generating dangerous hlorite, chlorate, and perchlorate, which can be harmful at sufficient doses. This article covers the pros and cons in comparison with other ozone IV treatments, safety limitations, and the latest clinical evidence. Please note that this article is to provide evidence-based information, not to encourage any specific treatments. 

Section 1: Mechanism, Chemistry, and Clinical Evidence

Biochemical Dynamics of Ozonated Saline Infusion

The ozone saline drip begins with medical-grade ozone being bubbled through sterile 0.9% sodium chloride (NaCl) for 10 to 20 minutes before and during the drip.

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Unlike major autohemotherapy and other blood ozone treatments, where blood's natural antioxidant buffering capacity moderates the reaction, saline lacks these protective proteins. As a result, the drip delivers dissolved ozone (O₃), hydrogen peroxide (H₂O₂), and reactive oxygen and chloride species directly into your vein [2,1]. This distinction is what gives the ozone saline drip its unique pharmacological profile compared to blood-based ozone methods.

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Safety testing of the ozone-saline interaction is a critical consideration. The safe ozone concentration for ozone saline drip (typically 3 to 10 µg/mL) is much lower than what you’d use in any blood ozone treatments. 

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Also, ozonated saline has some potentially harmful chlorinated byproducts such as chlorite, chlorate, and perchlorate [2,1]. 

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In addition, the pharmacokinetics of ozonated saline demand rapid administration. Ozone concentration in the prepared solution decays quickly after bubbling ceases, meaning the drip should be administered immediately to deliver the intended dose to the patient[1].

Differences Between Ozonated Saline Infusion and Autohemotherapy

Understanding the key biochemical differences between intravenous (IV) ozonated saline and ozone autohemotherapy (O3-AHT) requires examining how ozone interacts with biological substrates in each method, as the reaction environment fundamentally shapes the downstream molecular effects.

Autohemotherapy

In major autohemotherapy (MAH), a volume of blood (typically 100–200 mL) is drawn into an anticoagulated container and mixed with a precise ozone/oxygen gas mixture outside the body. This is the most extensively studied method in the clinical literature.

Upon direct contact with whole blood components, ozone and oxygen react within seconds to the full spectrum of blood substrates, including:

• Plasma lipids
• Albumin
• Antioxidants (glutathione, ascorbic acid, uric acid)
• Red blood cell membranes, white blood cells, and platelets

Ozone reacts with polyunsaturated fatty acids in plasma and cell membranes, generating reactive oxygen species as early, short-lived messengers and lipid oxidation products (LOPs), including lipid peroxides, 4-hydroxynonenal (4-HNE), and ozonides. These LOPs act as controlled, low-level oxidative stress signals.

With MAH, the clinician can precisely control the ozone concentration per mL of blood, and the reaction is completed before the treated blood re-enters circulation. This makes the dose-response relationship more predictable.

IV Ozonated Saline

In IV ozonated saline, ozone gas is bubbled through sterile normal saline (typically 0.9% NaCl) until a target dissolved ozone concentration is reached. This ozonated saline is then infused intravenously.

Normal saline lacks the biological substrates present in whole blood. There are no lipids, no albumin, no antioxidants, no blood cells in the saline itself. Ozone dissolved in saline exists primarily as molecular ozone (O₃) and its aqueous decomposition products, including reactive oxygen species such as hydroxyl radicals (·OH), superoxide anion (O₂·⁻), and hydrogen peroxide (H₂O₂). Each of these species is naturally occurring in the human body and performs a specific role [3]. Among them, hydrogen peroxide is the most stable one, which is most likely to last long enough to affect your physiology.

While MAH generates LOPs as key secondary messengers through lipid ozonation, IV ozonated saline delivers primarily dissolved ozone and H₂O₂ directly into the venous blood. The ozone and ROS then react with blood components in vivo (inside the body) rather than ex vivo, generating a smaller amount of LOPs and activating Nrf2.

This makes H₂O₂ the dominant mediator in ozone saline drip. Given the rapid decomposition of ozone and other oxidative species in aqueous solution, hydrogen peroxide (H₂O₂) is likely the predominant reactive species. 

Theoretically, hydrogen peroxide and other oxidative molecules in ozonated saline can theoretically influence other aspects of your physiology, including [3]:

• Temporarily improving insulin function (this is typically observed across most biooxidative therapies)
• Initiating wound healing signals
• Supporting protein folding
• Influencing inflammatory balance

Ozone Saline Drip: The Clinical Evidence

Ozone saline drip studies have been published as part of various retrospective studies and case series, especially during the pandemic, especially in India and Europe. Most prepandemic mechanistic and randomized controlled trials are Russia-based studies. Overall, moderate-quality evidence supports clinically meaningful benefits, especially in combination with standards of care.

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A retrospective study by Sharma et al. evaluated IV ozonized saline as COVID-19 prophylaxis for healthcare workers (N=64) in a dedicated hospital setting. When compared to health care workers who just received standard prophylaxis, the combination with ozone resulted in significantly lower positive tests [4]. MODERATE

In a single-arm pilot clinical study, Schwartz et al. administered IV ozonized saline solution (200 mL at 3–5 µg/mL daily for 10 days) as a complement to standard care in 25 hospitalized adult patients with mild to severe COVID-19 at Virgen De La Paloma Hospital, Madrid. The authors reported a tendency toward clinical improvement (reduced dyspnea, weakness, and body temperature), improvements in laboratory markers (D-dimer, fibrinogen, LDH, CRP), zero mortality, and no treatment-related adverse events[7]. MODERATE

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In a single-subject study, Thorp et al. administered IV ozonated normal saline (500 mL at 100 µg/mL) to one subject across seven paired hypoxia-chamber experiments (four with ozone, three without). They found that ozonated saline runs showed a 31% increase in hypoxia tolerance time (p<0.0001) and significantly longer time to oxygen saturation nadir (p<0.05), while control runs without ozone showed a 43% decrease in tolerance (p<0.0001). No infusion-related adverse events were reported [8]. PRELIMINARY

In a non-randomized comparative clinical study, Lebed et al. analyzed treatment outcomes in 98 post-operative brain tumor patients (51 receiving standard intensive therapy alone, 47 receiving standard therapy plus daily IV ozonated saline at 1.2–1.5 mg/L) alongside 30 blood donors as baseline controls. They found that ozone-treated patients demonstrated enhanced anti-edematous effects with periorbital edema resolution beginning by day 3 in most patients and in 100% by day 4. No specific adverse events were reported per group[9]. MODERATE

In a comparative study, Gretchkanev administered IV ozonated physiological saline (400 mL NaCl saturated at 400 mcg/L, five daily sessions) to 90 patients with threatened abortion as part of complex treatment, compared with 40 patients receiving conventional treatment only (total n=130, divided by trimester). Results indicated that the ozone group showed an approximately 22.1% increase in total plasma antioxidative activity, approximately 3.3x higher progesterone levels, 2.4–3.6x higher placental lactogen, a 20–50% decrease in circulating immune complexes, and clinically faster pain relief with reduced need for spasmolytics. No specific adverse clinical events were reported, and the authors noted that higher ozone concentrations (800 and 1200 mcg/L) produced adverse biochemical effects in vitro, supporting their dose selection[10]. MODERATE

In a randomized clinical trial, 118 patients with widespread progressive psoriasis (ages 18–66) were randomized into three groups: Group I (n=42, traditional therapy), Group II (n=42,  traditional therapy + IV O3SS [200 mL at 2.5 mg/L, mean 7.5 sessions]), and Group III (n=34, plasmapheresis + autotransfusion of ozone-modified erythrocyte suspension plus 200 mL ozonated saline as a bolus, mean 3.6 sessions). Results showed that ozone groups showed more pronounced and faster skin improvement, reductions in seromucoid and C-reactive protein, correction of coagulogram abnormalities, and normalization of lipid peroxidation. Group III was most effective, and ozone was well tolerated across groups[11]. STRONG

In a randomized clinical trial, 40 patients with obliterating atherosclerosis of the lower limb arteries (Fontaine stages IIA–IIB) were randomly divided into two equal groups: Group 1 (n=20) receiving standard conservative vascular therapy alone, and Group 2 (n=20) receiving the same baseline therapy plus daily IV infusions of ozonized physiological saline (400 mL at 4–7 mg/L). Results showed that ozone increased fibrinolytic activity and activation of the anticoagulant pathway, with a sustained hypocoagulative effect lasting up to 6 months[12]. STRONG

A randomized controlled animal study by Yang et al. studied 90 rabbits with VX2 tumors. Rabbits  were divided into three groups receiving intratumoral injections of normal saline (control), 20 μg/mL ozonated saline, or 40 μg/mL ozonated saline. Both ozonated saline groups showed significantly lower tumor growth rates and increased intratumoral necrosis compared to control, with the mechanism potentially partially mediated by elevated IL-6 and TNF-α[13]. MODERATE

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In a study focused on erythrocyte rheology, Katiukhin examined 42 patients (N=42) with complex pathologies who received a 7-day course of daily IV ozonated saline (200 mL at 2 mcg/mL). Using small sensors to detect force and pressure of passing blood cells, the study evaluated changes in the rheological (flow) properties of erythrocytes, including deformability and aggregation patterns, following the ozone saline drip course[5]. MODERATE

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The two human IV ozonated saline studies, Sharma et al.[4]  (N=64, COVID-19 prophylaxis) and Katiukhin[5]  (N=42, erythrocyte rheology), provide the most directly applicable evidence for this delivery method.  

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Preparation and Administration

Despite requiring no blood draw, ozone saline drip comes with its own risk. The World Federation of Ozone Therapy warns that ozone concentrations higher than 3 ug/mL may potentially create dangerous levels of chlorine-containing oxidative species [14], although clinical studies have used up to 10 ug/mL. Above 10 ug/mL, some clinicians report increased blood coagulation, which can be problematic [3].

Bubbling and Saturation Protocol

Medical-grade ozone is bubbled through 200 mL of sterile 0.9% NaCl for 10 to 20 minutes using an ozone-resistant glass flask. To achieve therapeutic saturation in the liquid, gas-phase concentrations are carefully controlled. For intravenous ozonated saline, the target dissolved ozone concentration in the final solution is typically kept at or below 5 to 10 mcg/mL[4]. This range is notably lower than concentrations used in other ozone delivery methods, reflecting the fact that saline cannot buffer reactive species the way blood components can. Bocci et al. reviewed the preparation of ozonated saline and emphasized that ozone-resistant containers and tubings (glass, silicone, or PTFE) are even more important, as standard plastics degrade on contact with ozone and may leach harmful byproducts [1]. 

Infusion Timing

Once the saline reaches saturation, the drip should be initiated immediately. The infusion is typically completed within a 15 to 20 minute window to minimize the decay of dissolved ozone, although some studies drip the ozonated saline over an hour. Some clinics continue to bubble the ozone through the saline during the drip. Any delay between saturation and infusion reduces the oxidative dose delivered to the patient.

Safety Monitoring and Concentration Limits

Clinicians must monitor the infusion site throughout the procedure for signs of local vein irritation or phlebitis. Because the ozone saline drip functions through a mechanism described as oxidative preconditioning, strict adherence to concentration limits is essential. 

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Since H₂O₂ can potentiate insulin action, ozone saline drip can lower blood sugar. So, healthy patients should be advised to eat prior to the treatment and clinics should be ready to treat hypoglycemia. 

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Contraindications to the ozone saline drip include glucose-6-phosphate dehydrogenase (G6PD) deficiency, active hyperthyroidism, severe anemia, and any active bleeding disorder. Patients with a history of thrombophlebitis should be assessed carefully before intravenous access is established.

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This content is for educational purposes and does not constitute medical advice.

References: 

1 Bocci, V. (2010) The actual six therapeutic modalities. In OZONE, pp 35–74, Springer Netherlands, Dordrecht

2 Ma, L., Wen, S., Yuan, J., Zhang, D., Lu, Y.-L., Zhang, Y., et al. (2020) Detection of chlorite, chlorate and perchlorate in ozonated saline. Exp. Ther. Med., Spandidos Publications 20, 2569–2576

3 Sies, H., Berndt, C. and Jones, D. P. (2017) Oxidative stress. Annu. Rev. Biochem., Annual Reviews 86, 715–748

4 Sharma, A., Shah, M., Sane, H., Gokulchandran, N., Paranjape, A., Khubchandani, P., et al. (2021) Intravenous ozonized saline therapy as prophylaxis for healthcare workers (HCWs) in a dedicated COVID-19 hospital in India - A retrospective study. Eur. Rev. Med. Pharmacol. Sci., Eur Rev Med Pharmacol Sci 25, 3632–3639

5 Katiukhin, L. N. (2016) Influence the course of treatment injections of ozonated saline on the rheological properties of erythrocytes in patients with complex pathology. Fiziol. Cheloveka, Pleiades Publishing Ltd 42, 100–105

6 Sharma, A., Shah, M., Lakshmi, S., Sane, H., Captain, J., Gokulchandran, N., et al. (2021) A pilot study for treatment of COVID-19 patients in moderate stage using intravenous administration of ozonized saline as an adjuvant treatment-registered clinical trial. Int. Immunopharmacol., Elsevier BV 96, 107743

7 Ozone in COVID-19 https://jppres.com/jppres/ozone-in-covid-19/

8 Thorp, J. A., Hollonbeck, S. A., Viglione, D. D., Green, P. C., Hodge, J. R., Tamburro, J. A., et al. (2020) Novel therapy for COVID-19 does intravenous ozonated-saline affect blood and tissue oxygenation? J. Gynecol. Res. Obstet., Peertechz Publications Private Limited 6, 046–050

9 Лебедь, С. Л. (2005) Патофизиологическое обоснование применения озонированного физиологического раствора в послеоперационном периоде у больных с новообразованиями головного мозга, кандидат медицинских наук, Нижний Новгород

10 Gretchkanev, G. O. (2001) Ozonetherapy as the main component of the complex treatment of threatened abortion

11 Викторович, Б. В. (2011) Эффективность озонотерапии в комплексном лечении псориаза. Вестник Российского университета дружбы народов. Серия: Медицина 0, 97–102

12 Винник, Ю. С., Дунаевская, С. С. and Антюфриева, Д. А. (2016) ВЛИЯНИЕ ОЗОНИРОВАННОГО ФИЗИОЛОГИЧЕСКОГО РАСТВОРА НА СИСТЕМУ ГЕМОСТАЗА ПРИ ОБЛИТЕРИРУЮЩЕМ АТЕРОСКЛЕРОЗЕ СОСУДОВ НИЖНИХ КОНЕЧНОСТЕЙ. Vestn. St. Petersbg. Univ. Med. 11, 30–35

13 Ma, Q., Yang, C., Jiang, X., Liu, J., Shi, Y., Li, H., et al. (2018) Effectiveness of ozonated saline in the treatment of VX2 tumors in rabbits. J. Interv. Med., J Interv Med 1, 143–149

14 Feng, H. X. and Baeza-Noci, J. (2017) Ozonated saline solution and ozone therapy, World Federation of Ozone Therapy, Bologne