Milestones of Medical Ozone

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Milestones of Medical Ozone

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Renate Viebahn-Haensler

Nordring 8, D-76473 Iffezheim, Germany

Paper presented at the 15 th Ozone World Congress of the International Ozone

Association in September 2001 in London

Medical Ozone as a Focal Point of Criticism

If we could either press medical ozone into tablets, pack them at the right

dosages, or store it in the form of stable infusion solutions, or even sell

it as an OTC product - many of our problems would be solved. Since its

discovery by SCHÖNBEIN in 1839, ozone, and particularly medical ozone, has

always

had a negative image. This was why, already in 1935, JUSTUS VON LIEBIG proposed

calling this Janus-like substance " ozonized oxygen " to make it less

offensive. Although this sounds better, its Janus-headed nature still remains.

Since the introduction of ozone therapy into medicine during the 1950s, its

value or " non-value " have been subject to heated and controversial

discussions. And, naturally, particularly in the field of biological therapy

methods,

charlatans have found a nesting place again and again. It is against these

that ozone therapy has most certainly had and still has a running battle to

fight.

 

Nowadays, ozone therapy is understood to be a genuine treatment method in

complementary medicine, encouraging the scientific dialog between traditional

medicine and complementary methods. Critical discussions have activated basic

research in the field of ozone therapy including the revision of highly

complicated treatment methods and resulting in the exclusion of intravascular

administration of O2/O3 gas mixtures or infusions under pressure, and the

introduction of low-risk application techniques.

Guidelines on hygienic procedures in extracorporeal blood treatment with

ozone have been drawn up, and hygiene sets developed to guarantee the greatest

possible protection against infection and a safe use of medical Ozone.

Although large-scale placebo-controlled double blind studies have not yet

been conducted, we have a large number of case reports as well as controlled

clinical studies, that have been a great help to standardise dosages, treatment

regimens and application techniques. Ozone generators equipped with

photometric measuring units here fulfil the wide range of concentration and

dosage

requirements for the different indications.

State of the Art

Indications and underlying active mechanisms

Over the decades, a smaller but decisive number of indications for medical

ozone have crystallized, supported by a large number of case reports from

hospitals and practices. The underlying physiological active mechanisms of

ozone

have, for the most part, been clarified up to the present, and constitute a

plausible scientific background for its therapeutical application (see Table

1).

Table 1: The Indications for Ozone and its Underlying Active Mechanisms of

Action

Indications Mechanisms

External ulcers and skin lesions

Disinfection,Wound cleansing und Improved wound healing

Arterial circulatory disorders

Activation of RBC metabolism with an improvement of oxygen releaseActivation

of ROS (reactive oxygen species) and radical scavengers

Immunodeficiency and immunodysbalance eg

* Chronic forms of hepatitis B and C

* Supportive therapy in cancer patients

* Supportive therapy in rheumatoid arthritis

Activation of immunocompetent cells with release of cytokins such as

interferons and interleukins.

Modulation of the immune system

Increase of antioxydative capacity by activation of biological antioxidants

 

Inflammatory condition such as

* Knee arthrosis

* Gonarthrosis

* Traumatic knee disorders

Antiinflammatory effect

* Activation of antioxidative enzymes as radical scavengers

* Activation of immunocompetent and cartilage cells with release of

TGF-ß

Dental medicine

* Following tooth extraction

* Buccal infections (eg candida)

* Aphthae

* Parodontosis

Disinfection,Wound cleansing,Improved wound healing

 

Application forms

Medication forms in a gaseous state are somewhat unusual, and it is for this

reason that special application techniques have had to be developed for the

safe use of ozone. In local applications as in the treatment of external

wounds, its application in the form of a transcutaneous O3 gas bath has

established itself as being the most practical and useful method, for example at

low

(subatmospheric) pressure in a closed system guaranteeing no escape of ozone

into the surrounding air. Ozonized water, whose use is particulary known in

dental medicine, is optimally applied as a spray or compress.

Apart from rectal insufflation, principally used in the treatment of

intestinal conditions, but also applied systemically, autohaemotherapy [or

auto(haemo)transfusion] has established itself as the systemic therapy of

choice. A

corresponding dosage of ozone gas is passed through or, more correctly,

transferred (in the form of microbubbles) to 50 to 100 ml of the patient " s

blood in

a sealed, pressureless system, thus achieving the finest possible

distribution to reach the greatest possible number of red and white blood cells

with the

aim of activating their metabolism. In other words, the organism acquires

its own medication, the activated red blood cells and immunocompetent cells

then being reintroduced via normal drip infusion. This is a markedly low-risk

method when hygiene guidelines are observed, disposable units are used, and the

material is ozone-resistant.

In pain therapy for the locomotory system, ozone can be applied supportively

in the form of intramuscular or intraarticular injections.

Milestones in the Development of Ozone Therapy

The names A. Wolff, Payr and Aubourg will always be linked with pioneering

research, especially in the field of locally applied medical ozone. For

example, A. Wolff successfully treated putrescent wounds, suppurating bone

fractures, fulminating inflammations (phlegmons) and abscesses during the First

World

War, publishing his results already in 1915. This field then received a

major impulse through the work of the surgeon and ozone therapist Erwin Payr,

who

presented his epoch-making publication (of 290 pages) entitled " Ozone

Treatment in Surgery " (Ãœber Ozonbehandlung in der Chirurgie) at the 59th

Meeting of

the German Surgical Society (Deutsche Gesellschaft für Chirurgie) in 1935.

This can rightly be called the real beginning of ozone therapy. Even if the

actual methods have greatly changed, Payr already describes most of the

treatment methods known today. At the same time, the French physician Aubourg

established the " ozone enema " or rectal insufflation method, making use of its

local effect in infectious diseases of the intestine, as well as - already - its

systemic effect.

However, it was even further into the 20th Century, ie not until the 1950s,

that the use of medical ozone stayed forgotten. In particular, the absence of

ozone-resistant materials such as plastics, made it difficult for the

practitioner to apply ozone locally in treating wounds or via rectal

insufflation,

as any noticeable amount of ozone in the surrounding air made work

practically intolerable. When Hänsler presented his first medical ozone

generator in

1958, which was capable of producing an ozone / oxygen mixture at

therapeutically variable dosages (concentrations), and was able to make first

use of

ozone-resistant plastics, he could then, together with Hans Wolff, pave the way

for ozone therapy as we know it today.

Constantly basing his research on the considerable number of publications by

Payr and Aubourg, it was H Wolff who subsequently introduced extracorporeal

blood treatment into medical practice; Werkmeister developed local treatment

methods in the form of " subatmospheric ozone gas application " , and Rokitansky

- as a surgeon - presented the first comprehensive studies on the topical

and systemic treatment of diabetic gangrene. Knoch then introduced rectal ozone

insufflation into proctology, once more confirming its value in a controlled

proctitis study.

A large number of the indications described by Payr had been abandoned in

favour of other, more effective methods; in some indications medical ozone could

be applied complementary to a basic therapy. This particularly applied in

the case of rheumatism / arthritis and inflammatory diseases of the joints, for

which Fahmy has developed a wide therapeutical concept

Although relatively simple as regards application forms and active

mechanisms, the use of ozone in dental medicine developed very modestly. As

mentor, we

must here mention the Swiss therapist A. Fisch, who himself had made Payr

acquainted with ozone, and who presented a doctoral thesis (1952) and first

publication on the use of ozone in dental medicine in 1935. It was not until

the

end of the 1980s, though, that medical ozone once more became a subject of

dental research (Kirschner and Filippi).

Table 2 and 3 show the development stages of indications and applications,

effects and active mechanisms as milestones leading up to the present position

of ozone therapy (this list makes no claim of being complete).

Table 2: Milestones of Medical Ozone. Applications and Indications.

Applications and Indications References

Surgery

Topical treatments in: severely infected wounds, phlegmons, fractures,

highly infected, abscesses and fistulas

A. Wolff

E. Payr

1915

1935 Ozone enema as rectal insufflation of the ozone oxygen mixture in

proctitis, colitis and fistulas via silk catheters

P. Aubourg

1937

Medical Ozone Generator OZONOSAN

allows ozone application forms depending on ozone-concentration

J. Hänsler

1958

General Medicine

Major autohaemotherapy in the form of an extracorporeal blood treatment as

the beginning of a low risk treatment by avoiding intravascular gas

application forms

H. Wolff

1968

Surgery

Low pressure ozone gas application as a topical treatment for: decubitus

ulcers, diabetic gangrene, radiation fistulas and badly healing wounds

H.Werkmeister

1981

Diabetic gangrene, arterial circulatory disorders

O. Rokitansky

1982

Rectal application in proctitis and colitis

H.G. Knoch

1987

Orthopedics

Intraarticular injections in knee arthrosis, gonoarthrosis and rheumatoid

arthritis as supportive therapy

Z. Fahmy

E. Riva-Sanseverino

1981

1989 Dental Medicine

Use of ozonized water in disinfection, parodontosis, and wound healing

E.A. Fisch

R. Türk

1952

1976

Disinfection of rinsing systems in dental chairs

Epithelial wound healing

H.Kirschner, A.Filippi et al.

1991

A.Filippi

2001

Table 3: Milestones of Medical Ozone. Pharmacological Aspects

Pharmacological effects References

Ozone and human blood

Reactions of ozone with RBC components

Buckley et al

1975

Peroxide formation in full blood and plasma

Influence of ozone on RBC metabolism and other blood components in vitro and

in vivo

Washüttl et al

1977

Washüttl et al

1986

Ozone effect on human leucocytes and other immunocompetent cells

Induction of cytokins such as interferon-γ ,- ß, interleukins-1,2, 6 …. by

ozone in the form of extracorporeal blood treatment as " major

autohaemotherapy "

Leon, Bocci et al.

19981

Blut und Plasma

Activation of antioxydative enzymes and radical scavengers such as SOD,

G6PDH, GSH pox or GSHred…

as protective effect in reperfusion damage by free radicals

Leon, Bocci et al.

1990

Peralta et al.

1999

Biological models and protective effects of ozone

Ozone and prevention:

improvement of the survival rate in septic peritonitis by preventive ozone

application in an animal model and synergistic effect with different

antibiotics.

Schulz et al.

1999

Growth inhibitory effect on plasmodium falciparum in infected red blood

cells by pre-treatment with ozone

Lell et al.

2001

Pharmacological Aspects

Whereas the disinfectant properties of ozone, such as those known and

clinically applied in the treatment of wounds, for example, is in the meantime

able

to look back on a tradition of 100 years, a detailed knowledge of the

pharmacological properties of O3 is much more recent. The first investigations

on

the formation of peroxides in whole blood and plasma were conducted by the

work groups around Washüttl and coworkers, Buckley et al., Freeman et al. who,

in conjunction with the in vivo investigations by Rokitansky and Washüttl,

produced extensive clarity on the activation of red blood cell metabolism

through ozone.

Although Washüttl published the first investigations on immunoactivation by

the agency of O3, it was, in this case not until Bocci with his study on the

" Activation of Immunocompetent Cells by Ozone " that a breakthrough was made.

An initial publication in 1990 entitled " Studies on the Biological Effects of

Ozone 1: Induction of Interferon-? on Human Leukocytes " was followed by

" Studies on the Biological Effects of Ozone " numbers 2-12, which represent a

major milestone in ozone therapy up to this day:

The activation of immunocompetent cells via extracorporeal blood treatment

induces, after reinfusion, a cascade of immunological reactions - thus

constituting a basic pattern for explaining a major part of the indications

specific

to ozone therapy (see Table 1).

At the same time and in parallel to the studies conducted by Bocci, Peralta

and coworkers demonstrated the activation of antioxidants and radical

scavengers inherent to the organism. A preventive ozone application in the form

of

rectal insufflation produced an effective protection against reperfusion

damage in cases of hepatic ischemia (Peralta et al 1999).

Ozone and prevention is also the subject of a study on lethal peritonitis

first presented in 1999: a series of 5 preventive intraperitoneal ozone

injections reduced lethality from 95% to 35%. At a preventively applied O3

application (5 times before infection) in combination with the therapeutical

application of antibiotics (2 times after infection), it is even possible to

reduce

lethality by 80% or 100%. These are the first investigations on the synergistic

effect of ozone and antibiotics (Schulz et al 1999).

And finally, another, also preventive, effect of ozone has been found in its

ability to inhibit the growth of Plasmodium falciparum (the pathogen of

tropical malaria) in infected human red blood cells without visible haemolysis

(Lell et al. 2001).

Milestones in the Near Future?

Synergisms between the application of medical ozone and antibiotics open up

a whole new vista, and are intended to intensify the dialogue between

traditional and complementary medicine. Under the aspect of prevention, this

field

of indication might possibly change, ie new indications such as supportive and

preventive measures will be added to classical ozone methods used up to now,

and others abandoned.

A large-scale controlled clinical study, for example on chronic hepatitis B

or C would here constitute the first milestone in the foreseeable future.

References

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ameliorations cliniques notables par un traitement d´ozone " Bull. mem. Paris

140 :

644-645 (1936)

* Bocci, V., Paulesu, L. " Studies on the Biological Effects of Ozone.

1. Induction of Iinterferon-g on Human Leucocytes " Haematologica 75: 510-515

(1990)

* Buckley, R.D., Hackney, M.D., Clark, K., Posin, C. " Ozone and Human

Blood " Arch Environ Health 30: 40-43 (1975)

* Fahmy, Z. " Ozon-Sauerstofftherapie in der Rheumatologie " Proceedings

5. Ozon-Weltkongress (Wasser Berlin) 1981

* Filippi, A., Tilkes, F., Beck, E.G., Kirschner, H.

" Wasserdesinfektion zahnärztlicher Behandlungseinheiten durch Ozon " Dtsch

Zahnärztl Z 46: 485

(1991)

* Filippi, A. " Der Einfluss von ozoniertem Wasser auf die epitheliale

Wundheilung "

Dtsch Zahnärztl Z 56: 104-108 (2001)

* Fisch, E.A. " L´ozone en Médicine Dentaire " Semaine Dentaire 17 : 36

(1935)

* Freeman B.A., Miller, B.E., Mudd, J.B. " Reaction of Ozone with Human

Erythrocytes " in " Assessing Toxic Effects of Environmental Pollutions " (

Lee, D., Mudd, B. ed.) Ann Arbor Science Publishers : 151-171 (1979)

* Hänsler, J. " Gerät zur Entnahme von ozonhaltigem Gas mit Hilfe einer

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der Proktologie "

Aktuelle Koloproktologie 4: 161-173 (1987)

* Lell, B., Viebahn, R,. Kremsner, P. " The Activity of Ozone Against

Plasmodium Falciparum " Ozone: Sci Eng 23: 89-93 (2001)

* Léon, O.S., Menendéz, S., Merino, N., Castillo, R., Sam, S., Pérez,

L., Cruz, E., Bocci,V.

" Ozone Oxidative Preconditioning: a protection against Cellular Damage by

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Puig-Parellada, P., Gelpí, E., Roselló-Catafau, J. " Protective Effect of

Ozone Treatment

on the Injury Associated with Hepatic Ischemia-Reperfusion:

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* Riva-Sanseverino, E. " Knee-Joint Disorders Treated by Oxygen- Ozone

Therapy "

Europa Medicophysica 25: 163-170 (1989)

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* Schulz, S., Rodriguez, Z., Mutters, R., Bette, M., Menendéz, S.,

Carbajal, C., Hoffman, S. " Significant Increase on Survival in Lethal

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Symposium

Basel (1999)

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Erfahrungsheilkunde 25: 177-179 (1976)

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Erfahrungsheilkunde 26: 209-219 (1977)

* WashüttlJ., Viebahn, R. " Biochemische Aspekte der

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Ars Medici 5: 194-199 (1986)

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Mixtures "

Ozone: Sci Eng 11: 411-417 (1989)

* Werkmeister, H. " Ozon-Unterdruck Begasung bei chronischen

Ulcerationen "

Proceedings 5. Ozon Weltkongress ( Wasser Berlin) 1981

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" Dtsch Med Wschr 311 (1915)

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