Ozone therapy: notes on the infamous German safety study

Many ozone therapy proponents cite a “German study” into the safety of the treatment, which showed an extremely low risk of side effects based on over 5.5 million treatments. In fact, this appears to be misleading, and serious side effects including deaths have occurred over the years. Apparent causes of death have been gas embolism and allergic shock. The actual risk appears to still be fairly low for autohaemotherapy, though with possible remaining risk of allergic shock. I’m still in the process of translating these sources from German.

Regarding the widely-cited German study on safety:
https://www.g-ba.de/downloads/40-268-248/HTA-Ozon-Therapie.pdf pp 17-18

Side effects
Information on the risks and complications of ozone therapy is largely based on the dissertation by M.T. Attributed to Jacobs from 1982. The author calculated his results from the data provided by 23% of the 2,815 ozone therapists contacted. Thereafter, there were 336 incidents in 5,579,238 ozone applications (in 384,775 treated patients), of which 309 were “certainly” not due to “ozone per se”. In 27 “real” incidents, there were 3 eczematous skin reactions, 2 hypoglycemic conditions, 11 allergic reactions and 11 “unexplained cases” (including 1 death, 1 amaurosis). Jacobs calculated a side effect rate of 0.006%, “attributable to the substance ozone” was 0.0005%.
Eisenmenger criticized Jacobs’ calculations in 1986. A fundamental criticism was initially when there was doubt about the representativeness of the sample and the validity of the results. For example, no information on the basis of the success assessment shown was documented.
The main point of criticism, however, was the way in which the side effect rate was calculated. Jacobs based the incident rate on the millions of ozone applications, but not on the number of patients treated. If, as with drug side effects, the number of incidents is related to the number of patients treated, the incidence rate is between 0.1 and 0.2%. This quota would be considered to be questionable under pharmaceutical law.
In addition, publications on Jacobs’ work showed deviations from the data given in the dissertation, which are probably due to different, subjective conclusions drawn with regard to the relationship between ozone treatment and symptoms in the patient. This gives changing information on the number of incidents and deaths. The number of reported deaths directly related to ozone treatment varied between 1 and 6 patients. In contrast to the descriptions given above from Jacobs’ dissertation, Eisenmenger found the following tabular list of incidents in one publication:

• Deaths 6
• Visual disturbances 4
• Paraplegia 3
• Gas embolism in the pulmonary circuit 4
• Heart attacks 2
• Pulmonary embolism 4
• Apoplectic paralysis 2
• Cardiac arrhythmias 2

According to the previous publications, the criteria used to select 27 of the 336 incidents reported, the cause of which was assumed to be the substance “ozone per se”.
Further reports on various side effects (transmission of hepatitis C and AIDS pathogens; gas embolism, anaphylactic reactions, neurological symptoms, syringe abscesses) were later published. [i.a. Binder 96, Daschner 89,96,97; Eisenmenger 86; Gabriel et al. 96; Lüth et al. 83; Mattig et al. 87; Mayer 91; Oepen 89.92; Pencz 78; RKI 97; Roeckl 96; Schmitt 82]
The Committee draws the conclusion from the present publications on potential risks of ozone therapy that scientifically valid studies on the safety of the process are not yet available, but these are essential in view of the potentially fatal side effects of ozone therapy.

Eisenmenger W. Zur Ozontherapie. In: Oepen I, Prokop O, editors. Außenseitermethoden in der Medizin. Ursprünge, Gefahren, Konsequenzen. Darmstadt. Darmstadt: 1986, 195-220. https://core.ac.uk/reader/12167629

This article counters the claim of near complete safety, and lists a number of severe complications including deaths from apparent gas embolism or allergic shock (starting after the image of actress Jenny Jugo below). These followed direct gas injection, which is now regarded by many practitioners as malpractice; but even with autohaemotherapy (withdrawing blood, interacting it with oxygen-ozone, then re-injecting the blood) there remains a possible risk of allergic shock.

ON OZONE THERAPY
By WOLFGANG EISENMENGER

In recent years, ozone therapy has become known to a broad lay public, above all through reports in the daily press and in magazines. During the well-known naturopath Dr. jur. Köhnlechner described them as “the sharpest therapeutic weapon in the fight against circulatory disorders”, court experts and angiologists in trade journals have increasingly commented critically on this outsider method. The method is named after the ozone that is used in gas form. Ozone is a molecule composed of three atoms of oxygen with the chemical formula 03. It is created from oxygen in Ultraviolet radiation or electrical discharges and is a natural part of the earth’s atmosphere. Often the layman is also familiar with the smell of ozone, which can be perceived after lightning strikes and has led to the naming (ozein, Greek = smell). Ozone is extremely reactive chemically, since its decomposition produces molecular and nascent oxygen and because it supplies OH and OOH radicals in an aqueous environment. With organic compounds it can form ozonides, of which those of unsaturated fatty acids, sorbic acid and some terpenes are known. Large quantities of pure ozone were first produced in 1857 by Werner von Siemens using a tube generator. This principle is still used today for the production of ozone, whereby the development of ozone-resistant plastics today allows ozone to be produced in relatively compact and practical devices. Today, ozone has a wide range of applications, which has led to the establishment in 1973 of an “International Ozone Association” which deals with the production and use of ozone in nature and technology. The application in the treatment of drinking water and wastewater has become more well-known. The application in the medical field had its first beginnings in the second half of the 19th century. Jaroszyk [26] quotes e.g. Work from the years 1873/74 and 1888, in which the use of ozone in the treatment of malignant tumors is reported, whereby in one case ozonized water was injected into the surroundings of tumors, with the result of tumor regression.

The use of gaseous ozone in medicine goes back to A. Wolff [61]. The latter treated infected wounds during the First World War with an oxygen-ozone gas stream, whereby he claims to have had good results. The “crown witness” of ozone therapy was the Leipzig professor of surgery Payr. He had found contact with the ozone application through his own experience when in 1932 the dentist Fisch treated him with an ozone-oxygen injection into the pulp cavity because of gangrene pulpitis and Payr quickly became symptom-free. Payr then carried out experiments with ozone at his clinic, about which he reported both at the 59th meeting of the German Society for Surgery and in a publication [42]. In essence, he limited himself to the treatment of soft tissue infections when using ozone. In the pre-antibiotic era, these were cases where the limits of therapeutic success were reached. However, he also discussed intravenous use and administration for malignant tumors, sinus insufflations, intestinal insufflations, use for vascular occlusions, gangrene, rheumatism. A word by Payrs from his publication at the time can be found in a large number of new publications by ozone therapists: “What oxygen cannot do, ozone can do.”

Before the Second World War, there were further attempts at therapeutic use of ozone in France by Aubourg, in Switzerland by Bircher and at the Dermatological University Clinic in Munich, whereby the dermatologist Thieme clearly described successes and failures and described ozone as a good, irritant disinfectant, an analysis of the effort, time and costs had to decide on its further use. In the Second World War, therapeutic use does not appear to have been carried out on a larger scale, at least.

The “Renaissance” began after the war with the so-called hematogenous oxidation therapy according to Wehrli [57], briefly referred to as HOT, in which blood was oxygenated extracorporeally under UV radiation and then reinjected. Steinbart [51, 52] pointed out in the 1950s that the active principle of this treatment was based on the ozone generated by the UV radiation of the oxygen, and constructed a practical device for producing ozone. Soon afterwards, the physicist Hänssler developed other devices that were more widespread in the Federal Republic under the brand name “Ozo-nosan”. At the moment, newer devices from this manufacturer are called “PM 80”, “PM 81 D”, “PM 82 L “and” PM 83 K “on the market. Recently, another manufacturer has launched a device called” Bio-zomat “onto the market, especially for hyperbaric ozone therapy according to Kief.

The ozone application found its most active supporter in the internist Η. H. Wolff, became the chairman of the “Medical Society for Ozone Therapy eV” founded in 1972. His 1979 book> The Medical Ozone <[63] is generally referred to by ozone therapists as a basic source work. In it, Wolff gives a summary of the theoretical foundations and the therapeutic application of ozone and names the following types of application: subcutaneous, intramuscular, intravenous, intraarterial and intra-abdominal injections; Insufflations in the intestine, bladder, ureter, vagina; Fumigation of the skin; Injections in fistulas; extracorporeal introduction of ozone-oxygen mixtures (02/03) into the extracted blood with reinjection or infusion, depending on the amount of blood referred to as “small” or “large autologous blood treatment”. Ultimately, dentistry propagates the insufflation of ozone into root canals and the rinsing of inflamed tissue with ozone water as well as the introduction of instruments into ozone water.

The catalog of indications spans a wide range of ailments and diseases from many areas of medicine.

A compilation of the indications from the Vademecum for ozone therapy of the “Medical Society for Ozontherapy eV” is given in Table 1 by Oepen et al , coronary insufficiency and ulcer ventriculi et duodeni, lactation inhibition, kidney diseases of various origins, myocardial damage, condition after heart attack, dysmenorrhea, vegetative dystonia, therapy-resistant anemia, pylorospasm and dermatomycosis are no longer listed and fresh organ bleeding that is not directly accessible to ozone treatment. It is striking that, compared to previous indications, actinomycosis, cardiac and circulatory insufficiency with and without cyanosis, coronary insufficiency and ulcer ventriculi et duodeni, lactation inhibition, kidney diseases of various origins, myocardial damage, condition after heart attack, dysmenorrhea, vegetative dystonia, therapy-resistant Pylorospasm and dermatomycoses are no longer listed. Only two diseases in the literature are highlighted as contraindications: thyrotoxicosis and fresh organ bleeding, which are not directly accessible to ozone treatment.

Regardless of the proposals of the “Medical Society for Ozone Therapy e. V. “, there are numerous other indications in the ozone therapist literature. These include, for example, subcutaneous 02/03 injections for the treatment of migraines and cerebral circulatory disorders due to traumatic, apoplectic, arteriosclerotic and epileptic causes, use in cases of dyspnea with myogenic heart failure , Valve veins, angina pectoris and pulmonary emphysema. Astonishing successes are reported in Sudeck’s atrophy. For a number of years, ozone additive therapy for cancer patients has been added as a special indication area. Here Wolff mentions it as one of 10 points that were developed based on Seeger [48]. The use of ozone is mentioned here on an equal footing with the “suppression of all interference fields according to Huneke”, the administration of “preparations containing carcinoma antigens”, the injection of freshly extracted raw breast milk, the administration of mistletoe extracts, the ban on the absorption of glucose in all forms and the “omission harmful agents and methods, including cytostatics “.

Another key active principle is the chemical reaction of ozone with various substances in the human body. Wolff cites studies [11, 12, 49] that ozone weakens the effects of diastase, emulsin, pepsin, invertin, ptyalin, pancreatin and rennet, that is, it reacts with enzymes. Another target is the oxidation of free amino acids, according to Mudd et al. [37] specifically methionine and tryptophan. The same author assumes that ozone plays a role in the formation of peptide chains and that ozone reacts with nicotinamide coenzymes, whereby NADH is preferentially oxidized by ozone and, among other things, but only to a small extent, NAD is formed. From this, Wolff concludes that ozone in the NAD-NADH equilibrium causes a shift to NAD with the consequence of an increase in the willingness to reduce all metabolic steps. Furthermore, a special effect of ozone on unsaturated fatty acids in the blood with the formation of ozonides is postulated, based on studies by Albers [1,2], who examined the oxygen uptake of a linseed oil emulsion in vitro when adding erythrocytes, whole blood, plasma and ozone. Albers concluded from his results that there were inhibitors of oxidation in the blood which were destroyed by ozone. In connection with the formation of peroxides in the blood, the special effect on tumor cells is also discussed. Wolff [63] also points out the effect of ozone on other substances in the blood, such as creatinine, uric acid, pyruvate, protein and bilirubin. According to this, the total protein content is independent of the ozone, while uric acid, pyruvate, glucose and bilirubin decrease significantly depending on the ozone concentration used, i.e. would be broken down. Wolff also reports that the deformability of erythrocytes is increasing, referring to more recent literature [9], which describes membrane biochemical changes. The structure of the membrane lipids should be loosened by shortening the unsaturated fatty acids in the erythrocyte membrane, and the resulting ozonides should intervene in the glucose metabolism in the erythrocytes, with an increase in 2,3-diphosphoglycerate being attributed to the essential effect of the curative ozone effect. As the most important physiological effect, Wolff states that the oxygen partial pressure of the blood increases when ozone is given, so that a higher oxygen saturation of the blood is achieved.

The success stories of the ozone therapists are impressive. A work by Tabakova from the 3rd Surgical Clinic of the University of Sofia / Bulgaria [54] is cited particularly frequently. According to the study, 165 patients suffering from endarteritis obliterans, leg ulcers and varicosum, arteriosclerotic gangrene, diabetic gangrene and Raynaud’s disease managed to achieve an effective recovery in almost 98% of cases with obliterating vascular disease. The atonic ulcers were also healed with fumigation and injection with ozone. Wolff [64] reported 84% of excellent results in arterial circulatory disorders of stages III and IV according to Fontaine, and in 13% still moderate results. Ionescu u. Employee [22] reported an improvement in stage II to IV arterial circulatory disorders according to Fontaine in 54% of 46 cases and in 26% freedom from symptoms. Impressive success has also been reported with fumigation of skin lesions of different origins [59]. Constipation, ulcerative colitis, neurological diseases such as the condition after apo-plectic insult, liver diseases such as chronically aggressive hepatitis and also psychological symptoms were positively influenced according to various authors at the 1st International Ozone Therapy Congress. Biochemical parameters were also changed positively in vivo and in vitro. For example, reported a significant reduction in elevated cholesterol and transaminase levels in the blood and a significant reduction in uric acid levels [29].

Regarding possible complications and incidents, it had been claimed for years that the method was completely harmless. Although it was pointed out in individual publications that there were pressure sensations under the sternum, coughing and nausea after i.v. injection of 02/03, there were also reports of rippling noises above the heart after injection of 150 cm3 (!) of gas mixture into the cubital vein. In 1980, however, Wolff claimed at the 2nd Congress of the “Austrian Medical Society for Ozone Therapy” that there were no typical incidents caused by ozone. In the same year, the “Medical Society for Ozone Therapy e.V.” a survey of doctors and naturopaths to record observed side effects and incidents. The evaluation should be done as a dissertation.

Before the work was accepted as a dissertation by the relevant faculty, the results contained therein were partially published and used for argumentation. After that, out of 2,815 ozone therapists contacted – both doctors and naturopaths – 644 replied. They reported treating at least 384775 patients with a minimum of 5579238 ozone applications. 336 incidents were reported. The author analyzed that 309 of them were certainly not due to ozone per se, but rather reactions to e.g. B. Procaine preparations injected at the same time, hypocalcemic reactions to the administration of sodium citricum, result of defective technology such as air injection or intravascular, especially IV injection, which was too fast. 27 were then identified as real incidents, which were made up as follows: 3 eczematous skin reactions, 2 hypoglycanic conditions, 11 allergic reactions and 11 other unexplained cases, including one death and one case of bilateral amaurosis (blindness). It was concluded that the ozone application had a side effect rate of 0.006%, of which 0.0005% was due to the substance ozone. This incidence rate is surprisingly low compared to general serious drug reactions. However, after the publication of these results, a warning was given for the first time before the iv injection, since it is the most likely to cause an accident and offers no advantages over the “large autologous blood treatment”. Only in recent publications has this warning been formulated so clearly that the iv injection is considered obsolete or was called “malpractice” [17].

If one draws the conclusion from the previously cited representations of ozone therapists, it can be stated in a simplistic manner that, in the opinion of its users, ozone therapy is a method which has enormous positive effects, which are rarely achieved in medicine, according to statistical data, in a large number of cases Diseases of the most diverse etiology and pathogenesis are guaranteed and at the same time only cause a negligible number of side effects. If the latter occur at all, they can largely be traced back to mistakes made by the therapist. The application is so simple that the remedy or method is harmless even in the hands of the naturopath!

With all of this, the question arises, why ozone therapy must still exist as an outsider method and has not found its way into conventional medicine. It also remains incomprehensible why statutory insurance companies still refuse to include ozone therapy in their service catalog and why processes are being carried out to determine the effects and consequences of ozone therapy. The very last point was the reason why the method had to be paid attention to by forensic medicine. The first serious incidents did not become known, however, in connection with investigations by the public prosecutor, but because the press took care of them. In 1975, a well-known former film actress suddenly developed severe paralysis and emotional disturbances after intra-arterial injection of a 02/03 mixture, which only partially resolved (Fig. 1). This resulted in permanent damage to the left lumbar mark and additional spinal Brown-Sequard hemiplegia of D V / D VI. The case was taken up by the press because the treatment had been given by a well-known naturopath. Another issue of paraplegia after intra-arterial 02/03 injection, which has been associated with this naturopath, was dealt with in the magazine “Der Spiegel” in its No. 8, 1976.

It may be surprising that, for many years, no medical incidents after ozone therapy have been mentioned in medical literature and that the first specialist publication was preceded by reports in the lay press. One explanation can be found in the fact that even in large clinics, more than one serious complication was rarely treated within a manageable period of time, and that the clinical pictures that occurred under ozone therapy were also very difficult to interpret by differential diagnosis. Severe malfunctions of the central nervous system such as Passenger amauroses, which were observed several times after IV injection, were classified as hysterical blindness. In this context, a case from 1968 appears to be characteristic, when a 49-year-old patient after ozone injection with amaurosis and confusion was admitted to a Cologne clinic, whereby, as in later cases, considerable general changes were found in the EEG. The treating physicians considered the clinical picture to be an encephalitis of unknown origin after an unambiguous diagnostic clarification was not possible; the amaurosis was disqualified as psychologically.

Ozone therapy reached a forensic dimension when deaths were subjected to a forensic medical examination. The first such case occurred in Munich when, at the beginning of 1978, a 70-year-old woman became blind and passed out during an IV injection from 02/03 by a naturopath into the cubital vein. About three weeks later, the patient died of pneumonia in inpatient treatment. The neuropathological examination revealed numerous focussed softenings in the brain as with local circulatory disorders, with no pathological changes in the vessel wall being observed. An allergic shock and gas embolism were therefore discussed as the cause.

Just a few weeks later, a 33-year-old woman died in Schweinfurt in the practice of an alternative practitioner immediately after supposedly intra-arterial 02/03 injection. During the autopsy it was found that the injection was carried out intravenously. Since gas embolism could not be demonstrated and histologically there was allergic vasculitis, an allergic shock was assumed to be the cause of death.

At this time, incidents after ozone therapy were first mentioned in the medical literature. Pencz [43] reported on two cases: A 59-year-old patient had undergone complete amaurosis after i.v. injection of 15 ml gas mixture by a medical practitioner, combined with retrograde amnesia and impaired consciousness, which resolved after 6 days. The clinical picture corresponded to massive cerebral gas embolism. He also reported on a 72-year-old patient who had a complete spinal cross-sectional syndrome a few minutes after intra-arterial injection of an unknown amount 02/03 in both groin arteries and died a few weeks later. Pencz discussed here the cause of anterior spinal syndrome caused by an injection-induced vascular spasm or a drop in blood pressure.