**4. The extreme versatility of ozone therapy**

The sarcastic comment of the opponents is that ozone therapy looks like a panacea for all diseases. Indeed it seems so, but in reality this is due to the multitude of compounds originated at first from the reaction of ozone with body fluids, and eventually able to display pleiotropic effects delivered by different organs. For the sake of brevity we can only summarize the therapeutic effects so far reported


**Table 1.** Indiciations of Ozone Therapy in General

#### **4.1. Acute and chronic bacterial, viral and fungine infections**

Intuitively, ozone therapy is very useful in both acute and chronic bacterial, viral and fungine infections because the generated ROS are the natural and most effective agents to which even antibiotic resistant pathogens do not resist. [3-61] Moreover, improvement of metabolism and immunological functions contribute to a favorable outcome. Abscesses, anal fissures, fistulae, bed sores, furunculosis, inveterate osteomyelitis, vulvovaginitis, necrotizing fasciitis and torpid ulcers of various origin have been shown to improve rapidly, particularly using the combination of O3-AHT with topical treatment using either direct O2\_/O3 exposure or the cleansing and stimulating effect of ozonated water and oil. The activity of ozonated solutions in eliminating the infectivity and enhancing healing is almost unbelievable. However, in Western countries accustomed to the use of antibiotic creams (often with corticosteroids) there is no mental attitude to profitably use the inexpensive and most active ozonated oil. [62]

#### **4.2. Ischemic diseases**

It is observed that HO-1 is a protective enzyme allowing the formation of Fe2\_, bilirubin (an antioxidant) and carbon monoxide (CO), a vasodilator that, like NO+, increases the level of cyclic guanosine monophosphate, the reaction catalyzed by guanylate cyclase. Besides gases produced by the gut flora, it is truly remarkable that cells can release other gaseous molecules (NO+, CO and CO2), and it is even more surprising that even ozone can be produced by activated antibody-coated neutrophils. [60] These gases can now be considered as molecules

Excessive amounts of these molecules are toxic, causing serious pathological events and possibly death. Nature teaches us that these gases, depending on their concentrations, can be either friends or foes and similarly ozone therapy can be either useful or toxic. If this reasoning is correct, ozone therapy, when judiciously performed, is a simple, inexpensive and atoxic approach with the advantage of activating several biomechanisms in different cells unusually

The sarcastic comment of the opponents is that ozone therapy looks like a panacea for all diseases. Indeed it seems so, but in reality this is due to the multitude of compounds originated at first from the reaction of ozone with body fluids, and eventually able to display pleiotropic effects delivered by different organs. For the sake of brevity we can only summarize the

Dermatology Herpes Zoster and simplex, acne, eczema, lipodystrophy (cellulite), mycosis, psoriasis, atopic

Internal Medicine Hepatitis, diabetes, atherosclerosis, arterial hypertension, osteoarthritis, asthma, chronic

Dentistry Treatment of cavities, disinfection of cavities during surgery and post-operatory period.

Orthopedic Rheumatology Disc-radicular conflicts, disc herniation, articular rheumatism, lumbago, osteoarthritis, arthropathy, periarthritis, rheumatoid arthritis. Angiology Venous insufficiency, diabetic ulcer, arthropathy, coronaropathy, gangrene, postphlebitic

Gynecology Bacterial infections by protozoa or mycosis, Bartholin's cyst, vaginitis, menopause, chronic

Immunology Immuno-modulator, autoimmune disorders, adjuvant in treatments with radiation and in

bronchitis, gastritis, gastric ulcer, Crohn's disease, chronic constipation, hypothyroidism.

able to deliver crucial physiological and pharmacological effects.

leading to an integrated and often incredible response.

168 Pharmacology and Nutritional Intervention in the Treatment of Disease

**4. The extreme versatility of ozone therapy**

dermatitis

Nephrology / Dialysis Adjuvant in the treatment of ischemic-metabolic pathologies. Neurology Migraines, depression, vasomotor cephalea, neuro-vascular disorders.

Periodontitis, aphthas.

ulcer, peripheral vasculopathy.

pelvic inflammation, infertility.

immunodeficiency.

therapeutic effects so far reported

**Specialization Pathology**

**Table 1.** Indiciations of Ozone Therapy in General

Chronic limb ischemia (atherosclerosis, diabetes, Burger's disease) is most effectively treated at stage II-b with complete disappearance of pain and claudication. Moreover, since 1981, Rokitansky et al.[49] demonstrated that a cycle of O3-AHT (usually 14 treatments) led to a very good improvement in 70.6% and 53.8% of either stage III or stage IV (Fontaine) patients, respectively. Amputation of toes and limbs could be avoided in pre-terminal phases.

These results have been amply confirmed by Giunta et al.,[63] Mattassi et al. [64] and Tylicki et al.[65] Preterminal patients with chronic heart ischemia and no further susceptibility to conventional treatments have shown marked improvement after a cycle of 14 treatments of extracorporeal circulation of blood against O2\_/O3.[66] A randomized controlled study is in progress for establishing the validity of this more invasive method than classical O3-AHT.

#### **4.3. Age-related macular degeneration**

A 6-year study in 90 patients with the 'dry' form of ARMD has been carried out performing a cycle of 13\_/14 O3-AHT treatments. Mean distance best-corrected visual acuity was signifi‐ cantly improved in the treatment group of patients while in the control group, first treated with oxygenated autohaemotherapy, only a modest and not significant improvement in mean distance visual acuity was observed. No adverse effects have been noted and the patient's compliance has been excellent. [26] Owing to the constant increase of ARMD patients and the lack of an effective conventional treatment, this approach appears mandatory.

#### **4.4. Orthopedic diseases**

Until recently it was unthinkable that a mixture of O2\_/O3 could be useful in orthopedics. Indeed lumbar disk herniation and osteoarthritis, although having different etiologies, have a common inflammatory background expressed by a localized chronic oxidative stress due to excessive production of ROS, release of proinflammatory cytokines and activation of cyclo‐ xygenases. Common sense would proscribe the use of ozone, a master generator of free radicals and, as it is well shown, [34 – 67] after pulmonary exposure, a superb inflammatory agent. Contrary to all expectations, it is now well demonstrated [68] that combined intradiscal and periganglionic injection of medical ozone allows an excellent outcome in 70.3% of patients treated for disk herniation performed after conservative management failed to respond. In the same vein, it appears very surprising that the application of medical ozone in acute and chronic painful diseases of the joints allows rapid pain relief, disappearance of inflammation and improvement of mobility. Thousands of patients have been successfully treated and the lack of side effects is noteworthy. [69] These positive empiric observations need to be explained. Ozone is indeed a surprising gas that paradoxically, after prolonged administration at low concentrations, induces tolerance, a phenomenon termed 'hormesis' by Goldman [70] to indicate 'a beneficial effect of a low level exposure to an agent that is harmful at high levels'. Thus, at this stage, we use the definition of 'ozone paradox' for explaining these excellent therapeutic results. Immediately after O2\_/O3 administration in the nucleus pulposus or into inflamed endoarticular cavities; a sort of oxidative shock seems to subvert all the traditional rules by inducing an antioxidative response due to several factors, among which is the cholinergic antiinflammatory pathway. [71] A detailed discussion is reported elsewhere. (3)

hospitals, it would represent a small but important medical revolution able to cure or stabilize

General Aspects of Ozone Therapy http://dx.doi.org/10.5772/57470 171

There is no doubt that ozone can be toxic, and even today its hazardous employment by charlatans and unprepared physicians has contributed to a poor consideration of ozone therapy. That is one reason why the use of ozone is prohibited in some states of the USA and why this therapy is still regarded with skepticism by orthodox medicine even in Germany, where this approach was first conceived. Moreover, the following data tend to generalize that

**1.** Overwhelming evidence shows that the bronchial-pulmonary system is very sensitive to

**2.** This is very true because the respiratory tract lining fluid is constituted by a very thin, watery film containing a minimal amount of antioxidants that makes mucosal cells extremely vulnerable to oxidation. The opposite situation occurs for blood cells suspended in plasma, which has a potent antioxidant capacity (1.23\_/1.83 mmol/l) able to tame any

**3.** Saline-washed erythrocytes suspended in saline undergo extensive hemolysis after ozone

**4.** Cells in culture, even if exposed to very low ozone concentrations for a long time, undergo

**5.** One-hour exposure of saline-diluted blood to 5 mM of ozone induces genotoxic effects on

As a matter of fact millions of O3-AHT, even if performed in an empirical fashion during the past three decades, has neither yielded acute nor chronic toxic effects. According to Jacobs [76]

However, four deaths have been recorded due to pulmonary embolism, which occurred during direct intravenous administration of O2\_/O3, an application prohibited by the Euro‐ pean Society of Ozonetherapy since 1983. Thus ozone seems like Janus and his two faces require an explanation. This is now reasonably clear. Since 1988 we have investigated the problem in a scientific way using precise ozone generators, which allow checking ozone concentration in real time by a photometer calibrated with the classical iodometric method. A review [61] and a critical book (3) have extensively clarified the issue but this does not seem sufficient to dispel the dogma that 'ozone is always toxic'. However, we now consider ozone as a real drug that must be used with caution after having carefully defined its therapeutic window. First, the ozone must be calibrated against the antioxidant capacity of the patient's

several diseases in many patients in both rich and poor countries.

ozone is always toxic and should not be used in medicine:

ozone and this gas should never be inhaled. [67]

ozone dose within the therapeutic range (10\_/80 mg/ml).

this procedure has yielded the lowest number of medical complications.

blood in order to control the potential ozone toxicity

**6. Discussion and conclusions**

exposure. [12]

apoptosis. [74]

leukocyte. [75] *But is ozone always toxic?*

#### **4.5. Dentistry**

This is another medical specialty where ozone has been recently evaluated with exceedingly interesting results.[72] Primary root carious lesions are being treated with a novel ozone delivery system able to avoid any toxic risk for the mouth cavity and lungs. The tooth's lesion is exposed for 10\_/20 sec to a sort of ozone 'hurricane' based on a gas flow of 615 ml/min of O2\_/O3 at a low concentration (4 mg/ml), perfectly enclosed in a tightly fitting silicone cup enclosing the tooth. It is not surprising that all bacteria, particularly lactobacilli, are destroyed so that the ozone-sterilized dental surface becomes quickly remineralized, becoming hard and resistant to further bacterial attack. This new approach is simple, inexpensive and well tolerated, as opposed to the conventional and painful 'drilling and filling' management of primary root carious lesions. Dermatological, pulmonary, renal, hematological and neurode‐ generative diseases Owing to the ability of ozone to activate a number of biological targets, ozone therapy could be proficiently used in some dermatological, pulmonary, renal, hemato‐ logical and neurodegenerative diseases. However these pathologies so far have not been evaluated in a controlled fashion. Most of the patients with metastatic cancer resistant to radiotherapy and chemotherapy report a striking improvement of the quality of life with prolonged (twice weekly for months) O3-AHT treatments. [25 – 73] This is a constantly observed result, most probably due to a multifactorial neuroendocrine response.

#### **5. Summary**

Finally it must be emphasized that if ozone is judiciously used according to precisely defined guidelines, it causes neither acute, nor chronic side effects. After two decades of practical applications and the results observed in patients after conventional remedies have proved unsatisfactory. One has the feeling that, if ozone therapy could be accepted and used in all hospitals, it would represent a small but important medical revolution able to cure or stabilize several diseases in many patients in both rich and poor countries.
