Ozone is a gas which is an allotropic and a more active form of oxygen. The term comes from the Greek for stench since there  is an odor associated with ozone. Ozone is essentially oxygen with an extra molecule of oxygen making it O_3. Ozone (O₃) is heavier than regular oxygen (O₂). It quickly breaks down to oxygen (O₂) in approximately twenty minutes. The free atom released in the breakdown of ozone does have to attach to another gas and does so readily. It is this need to attach to another molecule of another gas or substance that we use in medicine.

Ozone in the atmosphere is formed when oxygen is exposed to the silent discharge of electricity. It can be both irritating to the pulmonary system and toxic in sufficient quantities. However, in ordinary medical quantities it is not irritating and, on the contrary, can be quite beneficial. Ozone only gets a bad name due to the fact that we use ozone as a measure of other ingredients in the atmosphere. It is usually not the ozone itself that is harmful but the other particles in the air that are harmful. Remember that we have technology to measure ozone but not all particles floating in the air. So, we use ozone to detect other particle presence.

Ozone has been in use in one form or another since the early 1900s. Its’ use has evolved as knowledge has evolved both commercially and medically. You will see much information available about self help procedures elsewhere. The ozone procedures done at this office are medical procedures.

However, usually there are also other medical problems and needs that need to be addressed that ozone alone will not help or solve. So, in this office we will evaluate the use of the procedure with your current health and medical problems.

Ozone is an antiseptic and disinfectant used in a variety of different places in modern society. It is used in swimming pools, hot tubs, municipal and home water filtration, air cleaners.

Ozone therapy in this country is relatively unknown. However, in other parts of the world it is used commonly. There is a clinical trial for asthma currently in the research stage here in the United States sponsored by the National Institute of Environmental Health Sciences with the location being at Johns Hopkins School of Hygiene and Public Health in Baltimore, Maryland.

Medical infusion procedures are able to extract the benefits of ozone and oxygen more directly than through other modalities such as the skin, pills or creams or other non medical procedures available to the general public. The procedures are generally not covered by insurance. However, your health is your own decision. It is also your decision how you spend the money that you earn.

Call this office and make an appointment to discuss your individual needs with the doctor. Each patient has individual problems and requirements which require medical evaluation.

Ozone in Medicine: Overview and Future Directions

By Gerard V. Sunnen, M.D.

Abstract:

Ozone, an allotropic form of oxygen possesses unique properties which are being defined and applied to biological systems as well as to clinical practice. As a molecule containing a large excess of energy, ozone, through incompletely understood mechanisms, manifests bactericidal, virucidal and fungicidal actions which may make it a treatment of choice in certain conditions and an adjunctive treatment in others.

Introduction

Ozone, best known for its protective role in the earth’s ecological harmony, and for its interaction at ground level with industrial pollutants, has unique biological properties which are being investigated for applications in various medical fields.

As early as the First World War, ozone’s bactericidal properties were used to treat infected wounds, mustard gas burns and fistulas. These first treatment attempts, however, were hampered by technological difficulties. Medical ozone generators have since been developed and refined. They differ from industrial generators in their capacity to deliver the purest ozone-oxygen mixtures in precise dosages. A critical advance in medical ozone technology was the development, in the early 60’s, of plastics which can adequately conduct this mixture and permit proper interfacing with patients. In the last few years ozone treatment has seen growing interest from diverse medical discipline, and research is in progress to delineate its effects on biological systems and to define its clinical applications.

Historical Perspectives

The history of ozone’s discovery is intrinsically entwined in the evolution of the earliest concepts in chemistry. Priestly and Cavendish noted that electrical sparks fired in a closed volume of air resulted in volume compression.[1,2] In 1785, Martinus Van Marum, subjecting oxygen to electrical discharges, noted “the odor of electrical matter” and the accelerated oxidation of mercury. In 1840, Schonbein repeated these experiments, concluded that this odor was due to a gas which he named ozone, from the Greek ozein (odorant), and described several of its properties.[3] Numerous researchers since that time have worked to elucidate the nature and actions of ozone. Still today, theoretical issues remain regarding its electron structure, the varieties of it molecular configurations and its kinetics. Mariniak and Delarive showed that it is an allotropic form of oxygen, and Mulliken and Dewar clarified its molecular architecture.[4]

In the latter part of the 19^th century, ozone was found to oxidize a spectrum of organic compounds and to interact with double bonds. Chemists made use of these properties to study complex molecules by cleaving them into smaller fragments. Harries, by such methods, discovered the structure of natural rubber.[4]

The ability of ozone to destroy toxic or noxious industrial impurities (phenols, cyanides, tetraethyl lead among others) and to inactivate bacterial contaminants in sewage has made it an attractive alternative to chlorination. Wiesbaden, Germany became the first city to use ozonation for purification of its drinking water (1901), followed by Zurich, Florence, Brussels, Marseille, Singapore and Moscow (the largest installation in the world), among others. The history of ozone’s medical applications has nebulous and anecdotal beginnings. Kleinmann is said to have carried out the first bacteriological studies on pathogenic organisms using the Siemens tube, shortly after its invention.[5] Payr,[6] and Fisch and Wolff[7] were clinician pioneers, and J. Hansler developed one of the first reliable models of medical ozone generators.[5,8]

Physico-Chemical and Biochemical Properties

 The oxygen atom exists in nature in several forms: (1) as a free atomic particle (O), it is highly reactive and unstable; (2) oxygen (O₂) its most common and stable form, is colorless as a gas and pale blue as a liquid; (3) ozone (O₃), has a molecular weight of 48, a density one and a half times that of oxygen and contains a large excess of energy in its molecule (P₃--) 3/2 O₂ + 143 KJ/mole. It has a bond angle of 127[3], which resonates among several forms, is distinctly blue as a gas and dark blue as a solid; (4) O₄ is a very unstable, rare, nonmagnetic pale blue gas which readily breaks down into two molecules of oxygen.

Ozone is a powerful oxidant, surpassed in this regard only by fluorine. Shonbein,3 in 1855, discovered that it reacts with ethelene. Exposing ozone to organic molecules containing double or triple bonds yields many complex and as yet incompletely configurated ephemeral transitional compounds (zwitterions, molozonides, cyclic ozonides), which may be hydrolyzed, oxidized, reduced or thermally decomposed to a variety of substances, chiefly aldehydes, ketones, acids or alcohols. Ozone reacts with saturated hydrocarbons, amines, sulfhydryl groups and aromatic compounds.

Of importance to biological systems is ozone’s interaction with tissue (especially blood) constituents. The most studied is lipid peroxidation although interactions have yet to be more fully investigated with complex carbohydrates, protein, glycoproteins and sphingolipids. These dynamics are especially relevant for medical applications because some of the most practiced methods in ozone therapy involve the mixing of a small volume of whole blood with a pure oxygen ozone mixture and subsequently returning it to the patient. In this manner, it is calculated that the dose of ozone administered will perform its therapeutic functions without disrupting blood constituents.

Since there are a variety of lipid components in whole blood, it is of more than theoretical interest to determine the end products of ozone per oxidation and their effects, not only on physiological systems but on the integrity of ambient patholgenic organisms, since one of the mechanisms of viral inactivation is thought to be through this modality. Cholesterol accounts for 120 to 220 mg/100 ml, of which 60% to 75% are cholesterol esters; phospholipids 9 to 16 mg/100 ml; triglycerides 40 to 150 mg/100 ml, and free fatty acids 6 to 16 mg/100 ml. Given a total lipid concentration of 450 to 1000 mg/100 ml and the large variety of lipid constituents, the possible end products of ozonation are bountiful.[9,10]

This question is further complicated by the presence of systems to buffer lipid peroxidation, including vitamin E, uric acid,[11] and enzymes such as superoxide dismutase, catalase, and the glutathione peroxidase system which has gathered the most experimental attention.[12]

Several agents derived from lipid peroxidation include free radical, singlet oxygen, hydrogen peroxide, hydroperoxide, ozonides, carbonyls, alkanes and alkenes. Of these, lipid hydroperoxides, the most extensively studied, are known in sufficient concentrations to manifest their toxicity by altering cell membranes. Acted upon by glutathione peroxidase, they are reduced to their corresponding alcohols.

Method of Manufacture and Precautions

The production of ozone-oxygen mixtures for human and veterinary applications is subject to important technical consideration and standards. Clinical ozone generators which regulate the flow of medical grade oxygen through high voltage tubes with outputs ranging from 4000 V to 14000 V are capable of producing precise ozone-oxygen mixtures within concentration ranges extending to 5%, predicated on three variables: (1) the voltage applied; (2) the oxygen flow rate; and (3) the electrode separation distance. The purity of the oxygen source is especially emphasized since nitrogen, in the presence of high energy fields, forms toxic nitric oxides.

Since the half life of ozone is 45 minutes at 20C (68F), losing its concentration to 16% of its initial value in two hours, it must be freshly generated for immediate use at the treatment site. The maximum dose generated, 5% ozone to 95% oxygen, is well below the explosive limit (15 to 20%). Caution is needed not to appose ether and an ozone, an especially reactive mixture.

Listed contraindications to ozone treatment[5] include acute alcohol intoxication, recent myocardial infarction, hemorrhage from any organ, pregnancy, hyperthyroidism, thrombocytopenia and ozone allergy.

Methods of Administration, Dosage, and Clinical Applications External Ozone Gas Application

Historically, ozone was first administered by application to external body sufaces to determine its effects on a variety of lesions, A. Wolff,[13] in 1915, is credited for using local ozone treatments for wounds, fistulas, decubitus ulcers and osteomyelitis. Like natural rubber which cracks and fritters when exposed to oxygen-ozone mixtures, early materials caused ozone to “bag” around skin surfaces and met with early oxidation disuse. Today, specially designed plastics (Teflon) enable extremities or portions of the head or torso to be comfortably encased in a space where a determined dosage ratio of oxygen to ozone is administered at a chosen flow rate. In this way, the walls of the transparent bags do not touch the patient, and important consideration in burn treatment.

Indication for external ozone application include poorly healing wounds, burns,[14] staphylococcal infections, fungal and radiation lesions, herpes simplex and zoster, and gangrene (diabetic or Clostridium). Dosage is adjusted to the condition treated. Gas perfusions may last from 3 to 20 minutes, ozone concentrations varying from 10 to 80 ug/ml (maximum five parts of ozone to 95 parts of oxygen). High ozone concentrations are used for disinfection and cleaning (or debridement), while low concentrations promote epithelialization and healing.[6,15]

Ozone Insufflation

Payr in 1935[6] and Aubourg in 1936[16] first used ozone-oxygen mixtures in rectal insufflation to treat ulcerative colitis and fistulae. The list of indications has expanded to include proctitis and hemorrhoids. It is reported that in inflammatory diseases of the bowel, ozone promotes healing and restores the flora balance disturbed by pathogenic organisms. In a typical treatment for ulcerative colitis, daily insufflations are applied starting with 50 ml in severe cases, increasing as tolerated in increments (till 500 ml), high concentrations administered initially (75 ug/ml) to achieve hemostasis, followed by low concentrations to promote resolution.[5] This technique may have some promise in the treatment of bowel infections associated with AIDS.

Microsporidia, a tiny, rarely detected parasite may be responsible for many cases of AIDS wasting illness,[17] and studies await determination of its susceptibility to ozone treatment.

Major Autohemotherapy (AHT)

Whereas it can be readily understood that external ozone applications produce local effects such as disinfection, wound healing or local circulatory enhancement, the technique of introducing ozone into the circulation poses more complex theoretical issues. In the technique of major autohemotherapy, 50 to 100 ml of blood is drawn from the patient, mixed with a dose of ozone-oxygen of a predetermined concentration, then returned via the same intravenous catheter (butterfly). Returned to the patient, the ozonated blood is rapidly distributed to all tissues.

In the treatment aliquot of blood, it is gauged that the dose of ozone given not only will exert therapeutic actions locally (virucidal activity, oxygenation, increased red cell fluidity), but will determine beneficial systemic actions.[18]

The duration of time that ozone remains in solution and its effects on endocrine, neurological, and immunological systems are not known. Clinically, some patients, upon receiving their own ozonated blood, report a faint background taste of ozone, which may be an indication of its survivability in solution for at least a few seconds.

Major autohemotherapy has been applied to the treatment of several conditions, including acute and chronic viral infections (hepatitis), some carcinomas, circulatory disturbances (diabetes, arteriosclerosis), and hyperlipidemia.[8,19-21] Added to a standard pharmacotherapeutic regimen for postmenopausal osteoporosis, this technique enhanced remineralization of bone.[22] Clinical reports however, need to be substantiated by properly designed studies. Of interest are the reports of some patients, who after receiving this treatment experience feelings of well-being lasting for a few minutes to several hours. Whether this represents a placebo effect, a metabolic alteration or possibly a neuropsychiatric mechanism remains to be determined.

Miscellaneous Applications

Although the above techniques of ozone administration represent the majority of hospital or office-based procedures, others deserve mention.

Minor Autohemotherapy

In this technique, 10 ml of venous blood is drawn from the patient, mixed with ozone-oxygen, then injected intramuscularly. Listed indications include asthma, acne, some allergic conditions and some carcinomas.[18,23,24]

Direct Intra-arterial or Intravenous Administration

Mostly of historical interest, this method was first used by Iacoste in 1951[25] for circulatory compromise and its possible sequelae (gangrene). Up to 10 ml of pure ozone-oxygen may be slowly injected directly into the artery (usually femoral), or into a vein, without incurring embolization since both gases are readily soluble in blood.[20] Indications include intermittent claudication, leg ulcers and cerebral vascular insufficiency. Due to accidents produced by too rapid introduction of the gas mixture into the circulation, this technique is now rarely used.

Intramuscular Injection

Up to 10 ml of pure ozone-oxygen mixture is injected into the gluteus maximus muscle or the deltoid. This treatment along with major autohemotherapy is invoked as an adjunct to cancer therapy.[15,18,26,27]

Ozonated Water

Ozone is approximately 10 times more soluble in water than oxygen. Mixed into aqua bidestillata (pyrogen free) water, the half life of ozone is nine to ten hours (at pH 7 and 20C); and at 0C, it is doubled. Ozonated water finds applications in dental surgery where it is reported to promote hemostasis, enhance local oxygen supply and inhibit bacterial proliferation. Applied following tooth extraction or during dental surgery,[28] it may also be rinsed in conditions such as thrush and periodontal disease, swallowed in cases of gastritis or gastric carcinoma, or irrigated in chronic intestinal or bladder inflammation.

Ozone Ointments

Ozonated olive oil provides long term, low dose exposure of ozone and lipid peroxides to tissues. Decubitus ulcers and mycoses are indications for its use.[29,30]

Balneotherapy

 Ozonated water bubbled in warm baths, provides stimulation of local circulation and disinfectant action to varicosities, peripheral circulatory disorders and dermatological conditions (eczema, ulcers).[5]

Blood Purification

The possibility of using ozone to sterilize blood supplies has been investigated by several authors.[7,31] The treatment of 500 ml of whole blood with 100 ml of O₃/O₂ mixture (40 to 50 ug/ml) is reported to render it virus-free without injuring any cellular elements. One study[31] examined 10,000 samples and found no cases of hepatitis transmission. This technique may extend its efficacy to the HIV virus as one preliminary unpublished study indicates although once ensconced in the genetic cellular material, it is unclear how any agent could inactivate it without compromising cellular integrity.

Metabolic and Physiological Effects of Ozone

 Most research on ozone’s biological effects have concentrated on pulmonary responses with emphasis on its toxicity. Interest has been keen on ozone’s role in ground level atmospheric pollution. Produced as a result of interactions between industrial gases, oxygen and ultraviolet rays, there is evidence of synergistic action on pulmonary compromise. The effects of pure ozone, however, need to be differentiated from those of smog.

The majority of studies have been performed on animals who show great interspecies variability in their response to inhaled ozone. Extrapolation to humans is difficult due to differences in pulmonary anatomy and physiology. Mice[32] seem to be the most sensitive (LD50, 22 ppm for 3 hrs) and birds[33] the least (turkeys survived 417 ppm ozone for 3 hrs). While overdose is marked by pulmonary edema and hemorrhage, long term, low level exposure produces poorly understood, sometimes contradictory findings.

 Reported effects[34] include enhanced enzyme activity, as evidenced by increase in glucose utilization, lactate and CO₂ formation and elevated glucose-6-phosphate dehydrogenase; an increase in the NADPH-cytochrome P-450 content in rat lung pointing to enhancement of metabolizing enzymes; increased lung fibroblast glucose uptake, and production of lactate and pyruvate.

Humans exposed to ambient ozone (0.24 ppm in room air for two hours) typically develop mild accelerated breathing in the context of symptoms such as tracheal or laryngeal irritation and chest tightness on inspiration. Large intersubject response differences are notable.[35] Athletes[36] performing moderate intermittent exercise show a 7% drop in Forced Vital Capacity (FVC) and a 15% reduction in Forced Expiratory Volume (FEV). The threshold for significant changes in respiratory compromise ranges from 0.15 ppm[37] to 0.25 ppm,[38] increasing ozone concentrations yield corresponding airway hyper-responsiveness through bronchoconstriction. Histological findings extrapolated from primate research points to ciliated cell inhibition and type 2 cell proliferation, increased membrane permeability and variable inflammatory response.[12] Reported biochemical alterations[39] include increased oxygen consumption and glucose utilization; activation of NADPH, superoxide dismutase, GSH peroxidase, GSH reductase and glutathione peroxidase. Pulmonary effects from ozone in low doses appear to include metabolic activation of lung cells while higher doses produce evidence of cellular metabolic compromise.

 In the methodology of ozone treatment, care is given to avoid the escape of ozone into the treatment area and modern machines are equipped to catalytically convert excess ozone to oxygen during administration. Interestingly some studies point to possible beneficial effects of low dose ambient ozone.[40,41] The phenomenon of ozone tolerance or adaptation the response to ozone exposure decreasing with time and finally evolving to a plateau occurs in both humans and animals.[38] Its significance remains obscure.

For the reason that below 0.30 ppm the probability of ozone traversing the respiratory epithelium and entering the systemic circulation is so low, very few studies have attempted to measure these effects.[39] In the technique of major autohemotherapy and others that involve the direct introduction of ozone into the circulation, however, this question is of special relevance. Studies of human blood in young adult males exposed to 0.50 ppm ozone for 2-3/4 hours[42] show significant changes in erythrocytes (RBC) as well as in the serum. RBC membrane fragility, glucose-6-phosphate dehydrogenase and lactate dehydrogenase enzyme activities were increased, while RBC acetyl cholinesterase and reduced glutathione reductase were not significantly changed. Serum vitamin E and lipid peroxidation levels were significantly increased. These findings indicate that ozone exposure increases metabolic activation parameters in red blood cells.

 According to other researchers,[20,24,43] the direct intravascular injection of pure oxygen-ozone mixtures results in the following responses: (1) an activation of enzymes involved in peroxide or erythrocytes, an outgrowth of which is (2) stimulation of the[2,3] Bisphosphoglycerate cycle, shifting the oxyhemoglobin dissociation curve to the right thus releasing oxygen to the tissues. Further physiological effects include (3) an enhanced oxidative decarboxylation of pyruvate with the formation of Acetyl-CoA, and consequent citric acid cycle activation, (4) a direct influence on the mitochondrial transport system with reduction of NADH and oxidation of cytochromes, and (5) an increase in RBC pliability, blood fluidity, and arterial PO₂.

Mechanisms of Bactericidal, Virucidal and Fungicidal Action

 Although the inhibitory and lethal effects of ozone on pathogenic organisms have been observed since the latter part of the 19^th century, the mechanisms for these actions have not yet been satisfactorily elucidated. Ozone is a strong germicide needing only a few micrograms per liter for measurable action. At a concentration of 1 g/m3 H₂O at 1C, ozone rapidly inactivates coliform bacteria, staphylococcus aureus and Aeromonas hydrophilia.[44]

The inactivation rate of enteroviruses[45] is more rapid than for E. coli, takes place in relatively small concentrations of ozone, and is influenced by pH, temperature, and the presence of ambient organic compounds.

 Viruses differ in their susceptibility to destruction by ozone. The resistance of polio virus type 2 was 40 times that of coxsackie AS,[46,47] and in an experiment using a continuous flow mixed reactor under controlled laboratory conditions, relative resistance in descending order was found to be: polio virus type 2, echovirus type 1, polio virus type 1, coxsackie virus type B5, echovirus type 5, coxsackie virus type A9. In pure water, at maximal solubility of ozone and room temperature, Echovirus type 29 is inactivated in one minute, polio virus type 1 in two, type 3 in three and type 2 in seven minutes.

 The cell envelope of Gram negative microorganisms such as E. coli is a complex multiplayer system composed of an inner cytoplasmic membrane made of phospholipids and proteins invaginating into the cytoplasm, a peptidoglycan layer, and an outer membrane of  polymers such as polysaccharides. Gram positive cells have a less complex, three layer envelope with a thick peptidoglycan middle layer.

 The most cited explanation for ozone’s bactericidal effects centers on disruption of envelope integrity through peroxidation of phospholipids and lipoproteins. There is evidence for interaction with proteins as well.[48] In one study[49] exploring the effect of ozone on E. coli, evidence was found for ozone’s penetration of the cell membrane, reacting with cytoplasmic substances and converting the closed circular plasmid DNA to open circular DNA, which would presumably lessen the efficiency of bacterial proliferation. It is notable that higher organisms have enzymatic mechanisms to restabilize disrupted DNA and RNA, which could provide a partial explanation for why, in clinical treatment with ozone at doses prescribed, ozone appears to be toxic to infecting organisms and not to the patient.[50]

 Ozone possesses fungicidal effects, through poorly understood mechanisms. In one study, Candida utilis cell growth inhibition with ozone was greatly dependent on phases of their growth, budding cells exhibiting the most sensitivity to its presence.[51] Interestingly, in another study,[52] low doses of ozone stimulated the growth and development of Monilia fructagen and Phytophtora infestans, while higher doses were inhibitory.

 Viruses are parasites at the genetic level, separated into families based on their structure, type of nucleic genome and mode of replication. Many virions contain a phospholipid envelope with glycoprotein spikes, encasing the nucleocapsid which contains nucleic acids (DNA or RNA), and structural proteins (including enzymes).

 Lipid-containing viruses are sensitive to treatment with ether, assorted organic solvents, and ozone, indicating that disruption or loss of lipids results in impaired or destroyed infectivity. Viruses containing lipid envelopes include the Herpes viridae a large family grouping the Simplex, Varicella-Zoster, Cytomegalovirus and Epstein-Barr viruses; the Paramyxoviridae (mumps, measles); the Orthonyxoviridae (influenza); the Rhabdoviridae (rabies); and the Retroviridae (HIV). The HIV virus has an outer envelope made of a double layer of lipids penetrated by proteins of several types encasing two molecules of RNA.[53]

Many of the above viruses have complex, sometimes baffling life cycles and replicative strategies with progressions from host cell attachment of the virus particle, to penetration, uncoating of the viral envelope, synthesis of molecular components, and release of new generations of virions to the surrounding medium, most often through cell lysis. Many chronic viruses have eclipse phases alternating with phases of viremia, when waves of viral particles flood the bloodstream.

 In view of the above considerations, what part can ozone play as an antiviral agent? In one study,[46] polio virus 1 was exposed to 0.21 mg/liter of ozone at pH 7.2. After 30 seconds 99% of the viruses were inactivated (lost their ability to replicate within host cells), but appeared to maintain their structural integrity. Analysis of viral components showed damage to polypeptide chains and envelope proteins, which could result in attachment capability compromise, and breakage of the single-stranded RNA into two parts, producing replicating dysfunction at its root level. Other researchers[54] in similar experiments concluded that in ozonation, it is the viral capsid which sustains damage. It is to be noted however, that the polioviridae (Picornavirus family) contain four structural proteins encapsulating a single RNA strand and are devoid of lipids.

 In those clinical applications which make use of external (or body cavity) application of ozone, it can be appreciated that in view of the fact that a direct ozone-organism contact exists, inactivation of microorganisms, bacteria, viruses or fungi, proceeds by any one of a variety of different mechanisms. The treatment of burns, superficial mycotic infection, decubitus ulcers and abscesses is applied by this method. Theoretical issues present themselves, however, when examining treatment strategies aimed at systemic infections, notably viral afflictions which make use of introducing ozone-oxygen mixtures into the bloodstream (usually major AHT). The ozone-treated aliquot of blood which is reported to be rendered viral-free through direct contact with ozone and ozone peroxides,[5] is reintroduced into the circulation. Since very little free ozone remains in solution due to its high reactivity, it is its products mainly lipid compounds, possibly others which are thought to interact with circulating as well as tissue-bound virions, thus inactivating them.

Within the dose ranges prescribed (up to 10 mg (O3/100 ml of blood), we may be curious to measure this overflow antiviral capacity. Although unproven to be outright curative for any viral illness, ozone blood treatment, as reported in several studies[21,31,55] may lessen clinical severity or duration. Thus therapeutic benefits have been noted in hepatitis, acute and chronic, and herpes.[55] In chronic viral infections Cytomegalic, Epstein-Barr and Retroviridae (AIDS) among others blood ozonation performed in viremic cycles or in periods of clinical exacerbation may, through direct action, through the production of cofactors inhibitory to viral replication, or through modification of immune function, be used in inducing viral quiescence. Ozone is reported to be an immuno-stimulant in low doses and immuno-inhibitory at higher levels.[15,26,27]

It is not inconceivable, in view of the possibilities given to ozone’s antiviral properties that new generations of machines may be developed to test the therapeutic potential of the extra-corporeal treatment of circulating blood.

Ozone Treatment in Cancer

The logic sustaining the use of oxygen-ozone application to the treatment of carcinomas rests on the strategy of capitalizing on the disturbed metabolism of cancer cells. Since the first bio-chemical hypothesis of cancer was proposed by Warburg[56] in 1925; that all tumors have higher rates of glycolysis under aerobic conditions than do nontumor cells, efforts have been made to find the variations which could best affect treatment strategy. Although his statement has subsequently been amended considerably, there is a massive and evolving body of research centering on biochemical differences between normal and malignant cells.[57]

Some tumors have high rates of glucose use and lactic acid production in the presence of oxygen, a reflection of a number of possible mechanisms, from membrane transport differences to variations in ATP regulation. Cancer cell mitochondrial ribosomes have altered J structure and function which could diminish their oxidative energy producing abilities thus accounting for their limited aerobic potential.[57]

 Some authors[5,26] report a peroxide intolerance in tumor cells. Possessing insufficient catalase and peroxidase, they are incapable of effective peroxide inactivation. Such cells exposed to ozone are said to show a significant decrease in lactate content, indicating that ozone may induce metabolic inhibition in some carcinomas.

 In one study,[58] cultured cells of different carcinoma types were compared with non-cancerous human lung fibroblasts on exposure to ozonated air (0.3, 0.5, and 0.8 ppm of O₃ for 8 days). Alveolar (lung) adenocarcinoma, breast adenocarcinoma, uterine carcinosarcoma and endometrial carcinoma showed 40% cell growth inhibition at 0.3 ppm and 60% at 0.5 ppm. The non-cancerous lung cells were unaffected at these levels. In 0.8 ppm exposure, cancer cell growth inhibition was 90%. Interestingly, it was at this level that the control cell group started to manifest anabolic slowdown (50%). The authors postulate that cancer cells are less able to compensate for the oxidative challenge of ozone than normal cells, possibly by way of a less functional glutathione system.

 There are many clinical and anecdotal reports,[21,25,27,59] of ozone major or minor autotherapy, at times prescribed on a daily basis for several weeks applied to the treatment of various carcinomatous conditions but with a paucity of controlled data. Several researchers have focused their efforts on using ozone as an adjunct to radiation or chemotherapy.[23]

Summary and Future Directions

 Ozone, an allotropic form of oxygen, possesses unique properties which are being defined and applied to biological systems as well as to clinical practice. As a molecule containing a large excess of energy, through incompletely understood mechanisms, it manifests bactericidal, virucidal and fungicidal action which may make it a treatment of choice in certain conditions and an adjunct to treatment in others. Although ozone’s medicinal effects were discovered in the 19^th century and clinically applied during World War I, equipment capable of purity and reliability of delivery of oxygen-ozone mixtures were not available until the late 1950’s. Since then, experience has accumulated for the administration of ozone to humans and animals via a variety of routes, in doses that are both nontoxic and relevant to clinical problems, externally in gaseous form (or in solution) and systemically in blood ozonation.

A review of a large body of literature is presented which describes a spectrum of therapeutic indications. Of these, ozone application for superficial infection, burns, dental and intestinal conditions, and possibly circulatory problems seem to be the most promising. As regards blood ozonation, further research is indicated to delineate the nature of its dynamics and the extent of its effectiveness in (1) the identification of the galaxy of compounds formed in this process which, in view of doses administered, by all evidence, have metabolic, immunological, endocrine and possibly neurological effects; (2) the purification of blood or blood components for transfusion purposes; (3) the inhibition of carcinomas with reference to the types which may be the most susceptible and to its use as an adjunct to radiation or chemotherapy; and (4) the inactivation or the repression of viral diseases with special attention to chronic conditions of the Herpes or Retroviridae (HIV) families.

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27.  Zabel W: Ganzheitsbehandlung der gaschwulsterkrankungen. Hippokrates 1960;3 1:751-760.

28.  Turk R: Ozone in dental medicine. Ozonachrichten 1985;4:61-65.

29.  Schulz S: Ozonisiertes olivenol-experimentelle ergbnisse der wundheilung am tiermodell. OzoNachrichen 1982;1:29.

30.  Washuttl J, Viebahn R: ozonisiertes oliveolozusammensetzung und desinfizierence wirksamkeit. OzoNachrichen 1982;1:25.

31.  Wehrli R: Transact six. Ham 1957;318

32.  Mittler S, King M, Burkhardt B: Toxicity of ozone. AMA Arch Ind Health 1957;15:191-197.

33.  Clamann H: Physical and medical aspects of ozone, in Physics and Medicine of the Atmosphere and Space. John Wiley and Sons, New York, 1960,p. 151.

34.  Basset D, Bowen-Kelly E: Rat lung metabolism after 3 days of continuous exposure to 0.6 parts-per-million ozone. Am J Physiol 1986;250 (2 Part 2): E131-E136.

35.  McDonnell W, Horstman D, Abdul-Salaam S, House D: Reproducibility of individual responses to ozone exposure. Am Rev Respir Dis 1985;131(1): 36-40.

36.  Folinsbee W: Effects of ozone exposure on lung function in man: A review. Rev Environ Health 1981;3:211-240.

37.  Kulle TJ, Sauder LR, Hebel JK, Chatham MD: Ozone response relationships in healthy nonsmoker. Am Reu Respir Dis 1985;132(1):36-41.

38.  Hackney J, Linn W, Mohler J, Colier C: Adaptation to short term respiratory effects of ozone in men exposed repeatedly. J Appl Physiol Respirat Environ Exercise Physiol 1977;43:82-85.

39.  Melton CE: Effects of long term exposure to low levels of ozone: A review. Aviation, Space, and Environmental Medicine 1982;53:105-111.

40.  Dyas A, Boughton B, Das B: Ozone killing action against bacterial and fungal species: Microbiological testing of a domestic ozone generator. J Clin Pathol (Lond) 1983;36(10):1102-1104.

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TI:   Is There a Role for Medical Ozone in the Treatment of HIV and Associated Infections?

                               DT:   Sept. 1993

AU:   Michael T. Carpendale and John Griffiss

SO:   Rehabilitation Medicine and Research Services, Veterans Administration Medical Center, San Francisco, CA.

AB:   Medical Ozone inactivates many pathogenic viruses including HIV in vitro. Pilot studies in man suggest positive benefits in the early stages of HIV infection (T-4 cells greater than 400). These include increased T4 and T cells, normalizing of T4:T8 ratio, and a general feeling of well-being and minimal evidence of infection. Improvement also occurs in AIDS patients (T4 cells less than 200) but less evidence of T4 cell resurgence. These studies indicate that at least in vitro there is a good safety margin between the ozone dose required to inactivate HIV and the earliest suggestion of suppression of lymphocytes In fact, the lymphocytes are being stimulated at doses that completely inactivates HIV. More work needs to be done to clarify the most effective dosage and means of treating HIV infections with medical ozone.

Ozone Selectively Inhibits Growth of Human Cancer Cells

Science Vol. 209, 22 Aug 1980, pp. 931-933

Abstract:

The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as non-cancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The non-cancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.

24 April 1980; revise 11 June 1980.

TI:   Inactivation of Human Immunodeficiency Virus Type 1 by Ozone in Vitro

DT   9105

AU   Keith H. Wells, Joseph Latino, Jerrie Gavalchin, and Bernard J. Poiesz

SO   Blood, Vol. 78, No. 7 (October 1), 1991:pp 1882-1890

AB:   A device was designed to deliver a constant source of given concentrations of ozone to fluids containing human Immunodeficiency virus type 1 (HIV-1). Ozone was found to inactivate HIV-1 virions  in a dose-dependent manner. Greater than 11 log inactivation was achieved within 2 hours at a concentration of 1,200 ppm ozone. Similar concentrations of ozone had minimal effect on factor VIII activity in both plasma and immunoaffinity-purified preparations of factor VIII treated for the same time period. The data indicate that the antiviral effects of ozone include viral particle disruption, reverse transcriptase inactivation, and/or perturbation of the ability of the virus to bind to its receptor on target cells. Ozone treatment offers promise as a means to inactivate human retroviruses in human body fluids and blood product preparations.

TI   The Influence of Ozone on Tumor Tissue In Comparison With Healthy Tissue (in vitro)

DT   0789

AU   J. Washuttl, R. Viebahn and I. Steiner

SO   Ozone Science & Engineering. Volume 12, pp. 65-72

AB:   In comparison with healthy tissue, freshly operated carcinomatous ovarial tissue was treated in vitro with ozone in a suitable medium using air as the reference. In an analogous test arrangement and for reference purposes, the cytostatics Adriblastin (= Doxorubicin, and adriamycin) and Holaxan (= Ifosfamide, a cyclophosphamide) were included for the tumor tissue. After preparation of the tissue samples, the following substances were examined: 2, 3-DPG, NAD (Nadide, DPN), Lecithin, Lysolecithin plus different enzymes and metabolites both in the mitochondrial fraction as sell as, in the supernatant layer, the following: LDH, HBDH, Aldolase, ICDH, F-6-PK, cytochrome oxidase, Na, K, Ca and peroxidic metabolites.

Statistically significant changes were found in tumor tissue after the action of ozone in the mitochondrial fraction in the case of  NAD and 2, 3-DPG, and in lysolecithin were the supernatant substances were concerned; this only applied to supernatant NAD in the case of healthy tissue.

In all other parameters examined, no form of statistical change was found whatsoever in either healthy or tumorous tissue.

[Ozone therapy in lumbar sciatic pain]

[Article in Italian]

D’Erme M, Scarchilli A, Artale AM, Pasquali Lasagni M

Istituto Chirurgico Ortopedico Traumatologico (I.C.O.T.), Latina. Pa4504@pan-service.it

 INTRODUCTION: Medical ozone is a mixture of oxygen and ozone which can be used for several medical applications. Ozone was first applied clinically to the treatment of lumbar sciatic pain peridurally, while Pietrogrande was the first in Italy to report on its intradiscal administration to treat nucleus polposus herniation. On account of these considerations, we have decided to introduce this method in our Institute (I.C.O.T. Latina) as an alternative to surgery in the treatment of lumbar sciatic pain supported by an intradiscal hernia.

MATERIAL AND METHODS: September, 1995, to April, 1997, we treated more than 1000 patients with intradiscal ozone infiltration. We prospectively analyzed the first 50 patients, with 6 months’ follow-up at least; all of them were preliminarily submitted to clinical examination, electromyography, CT and MRI. After local anesthesia, we injected the disk, with 18-20 G needles and under CT or fluoroscopic guidance, with 12 ml of a mixture of oxygen and ozone at a concentration of 20-30 micrograms/ml. The treatment was repeated two or three more times at intervals of 3, 15 or, when necessary, 30 days. After each treatment, CT follow-ups were carried out and the final follow-up was made 3 months later.

RESULTS: We divided our results into clinical and instrumental. As for clinical response, we had 68% positive results (40% excellent, 28% good) and 32% negative results (10% of patients underwent surgery and 22 are under medical and physical treatment). As for CT response, we had 82% positive results (36% excellent, 46% good), while no major changes between pre- and post-treatment CT findings in the remaining 18% of cases.

CONCLUSIONS: Ozone therapy, thanks to its ease of execution and noninvasiveness, permits the successful outpatient treatment of lumbar sciatic pain. Moreover, the lack of major complications and the good results obtained compared to other methods, such as chemonucleolysis, percutaneous automated discectomy, microsurgery and conventional surgery, suggest that ozone therapy can be considered the treatment of choice for lumbar sciatic pain and a valid alternative to surgery in many cases.

Warburg, Blass and Koch: Men With A Message.

G.A. Freibott

International Association for Oxygen Therapy

Priest River, ID, USA

“Today’s scientists have substituted mathematics for experiments, and they wander off through equation after equation, and eventually build a structure which has no relation to reality.”1

 “The scientists from Franklin to Morse were clear thinkers and did not produce erroneous theories. The scientists of today think deeply instead of clearly. One must be sane to think clearly, but one can think deeply and be quite insane.”2

 “But nobody today can say that one does not know what cancer and its prime cause is. On the contrary, there is no disease whose prime cause is better known, so that today ignorance is no longer an excuse that one cannot do more about prevention. That the prevention of cancer will come there is no doubt, for man wishes to survive. But how long prevention will be avoided depends on how long the prophets of agnosticism will succeed in inhibiting the application of scientific knowledge in the cancer field. In the meantime, millions of men must die of cancer unnecessarily.”3

"All truth passes through three stages:

First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as self-evident."4

These quotes are the frank opinions of the Father of Alternating Current; A two time Nobel Laureate; and a nineteenth century German philosopher, Warburg, Blass, Koch and Tesla were men whose truths are becoming evident in today’s world of science. These were pioneers and scientists of the highest magnitude. This abstract uncovers, postmortem, the discoveries of these men and their contributions to future scientific studies.

Otto Warburg, won his first Nobel Prize in 1931 for the oxygen transferring enzyme of cell respiration and his second Nobel Prize in 1944 for his discovery of the hydrogen transferring enzyme. His discoveries are quoted above and as follows:

“But, even for cancer, there is only one primary cause. Summarized in a few words, the nine cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”6

 “Because no cancer cell exists, the respiration of which is intact, it cannot be disputed that cancer could be prevented if the respiration of the body cells would be kept intact.”7

Dr. F. M. Eugene Blass, an Oxidation Specialist and engineer/designer of the Pennsylvania Steel-Coke ovens, clinically verified Warburg’s foundational work. Returning to the United States in 1925, cured of his cancer and armed with the knowledge of the Institut fur Sauerstoff-Heilverfahren, Blass adamantly represented the German Kneipp/Nature Cure and Oxidative therapies.

 To illustrate:

“The recognizable results of an insufficient oxidation either because of a lack of minerals or oxygen or because of the presence of foreign matter in the bloodstream are the symptoms which bear the imposing nomenclature of modern “dis-ease”. The different kind of parasites, which are the “germs”, commonly blamed for the creation of these various symptoms find food and lodging, in the diseased soil which accumulates in the body but, logically, are not the cause of disease. A clean habitation will not tolerate such hospitality and normal vital fluids constitute the best insurance against sickness.”8

OXIDATION is the source of Life, it’s lack causes impaired health or disease, it’s cessation death.”9

 Dr. William F. Koch., MD, Ph.D., a well published pathologist and medical school professor, presented his co-practitioners with “a study of the phenomena of the free radical, the double bond, and its alpha placed hydrogen atom in the pathogenesis and correction of neoplastic, viral and bacterial diseases.”10

Quotes to illustrate further:

“’Oxidation has several positions of control in its process in line with our postulate. The first is the potency, of the FCG (functional carbonyl group) which must start the process by dehydrogenating the fuel. When this carbonyl group is not free, as when the hydrogen it removes from the fuel is not taken away by some electron acceptor system, then oxidation is blocked. And for this oxygen is essential as the ultimate electron acceptor in aerobic organisms. So lack of oxygen has two steps in blocking oxidation or hindering it.”11

 “Our postulate provides for the polymerization of the carcinogenic toxin as it develops to the cancer producing stage, and this provision is based upon the chemical and clinical circumstances that stare one straight in the face. Atrophy precedes neoplasia. If one answers that the neoplasia is a reaction to the atrophy stimulus as hay fever is to the pollen stimulus, one must still offer a mechanism for the reaction. The simplest mechanism that could be involved is that the toxin produces both changes, and this mechanism we have already explained as due to a block in energy production and transfer. Recovery from the states caused by the carcinogenic agent, be it virus or chemical, is therefore a satisfactory support to the contention, since the same agency accomplishes the corrections of all states, atrophy, pregrowth toxic state, cachexia, and the turnifactions.”12

 “After the pathogen, be it a virus, carcinogen, or some allergen has made the pathogenic integration, the need for oxygen in the diseased cells is all the more imperative, and removal of all sources of the pathogenic amines is the prime consideration. And not until a good dispersion of the tissue colloids is had, and a good oxygen supply is present in the cells should the reagent be given. For if it does not have a molecule of oxygen at hand to combine the free radical formed by each dehydrogenation, there will be no curative progression of oxidation, and the reagent is given in vain. This also applies to the free radicals produced by the use of the reducing agent.”13

“The best proof of the correctness or practicability of any postulate in medicine is doubtless the curative value of its application.”14

 REFERENCES:

1. Nicola Tesla, Radio Power Will Revolutionize the World, Modem Mechanix and Inventions, July, 1934, pg. 2.
2. lbid
3. Otto Warburg, The Prime Cause and Prevention of Cancer, 1969, pg. 16. (Translation by Dean Burk, National Cancer Institute.)
4. Arthur Schopenhauer, International Tesla Society Journal of Power and Resonance, Vol.5, No.4,19W, pg. 40.

• Otto Warburg, The Prime Cause and Prevention of Cancer, 1966, pg.6.
• lbid.
• F.M. Eugene Blass, Oxygen-Therapy-Blass: It’s Development into a Complete Uniform Treatment of Disease, Oxidation News Vol. 1, No.1, 1990 pg. 3.
• F.M. Eugene Blass, Oxygen Therapy: Its Foundation, -Aim and Results, 1927, pg. 1.
• W.F. Koch, The Survival Factor in Neoplastic and Viral Diseases, 1961, 1967. Front Cover.
• lbid.p.24.
• W.F. Koch, Survival Factor in Neoplastic and V-um Diseases, 1961,1967, P. 2s7.
• W.F. Koch, Neoplastic and Viral Parasitism, Their Basic Chemistry And Its Clinical Reversal. (An Introduction to Free Radical Therapy 1967 ppg. 41-42.
• W.F. Koch, Survival Factor in Neoplastic and Viral Diseases, 1961, 1967, p. 257.