Ozone: Science & Engineering

The Journal of the International Ozone Association

ISSN: 0191-9512 (Print) 1547-6545 (Online) Journal homepage: http://www.tandfonline.com/loi/bose20

Ozone in Medicine: Clinical Evaluation and

Evidence Classification of the Systemic Ozone
Applications, Major Autohemotherapy and Rectal
Insufflation, According to the Requirements for
Evidence-Based Medicine

Renate Viebahn-Hänsler, Olga Sonia León Fernández & Ziad Fahmy

To cite this article: Renate Viebahn-Hänsler, Olga Sonia León Fernández & Ziad Fahmy
(2016): Ozone in Medicine: Clinical Evaluation and Evidence Classification of the Systemic
Ozone Applications, Major Autohemotherapy and Rectal Insufflation, According to
the Requirements for Evidence-Based Medicine, Ozone: Science & Engineering, DOI:
10.1080/01919512.2016.1191992

To link to this article: http://dx.doi.org/10.1080/01919512.2016.1191992

Accepted author version posted online: 23

May 2016.
Published online: 23 May 2016.

Submit your article to this journal

Article views: 19

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=bose20

Download by: [Hacettepe University] Date: 27 June 2016, At: 13:51

 OZONE: SCIENCE & ENGINEERING
http://dx.doi.org/10.1080/01919512.2016.1191992

Ozone in Medicine: Clinical Evaluation and Evidence Classification of the

Systemic Ozone Applications, Major Autohemotherapy and Rectal Insufflation,
According to the Requirements for Evidence-Based Medicine
Renate Viebahn-Hänslera, Olga Sonia León Fernándezb, and Ziad Fahmya
a
Medical Society for the Use of Ozone in Prevention and Therapy, D-76473 Iffezheim/Baden-Baden, Germany; bPharmacy and Food Institute,
University of Havana, Havana, 10 400 Cuba

ABSTRACT ARTICLE HISTORY

Now that indications are clearly defined, applications have mostly become standardized and the Received 11 April 2016
active mechanisms have been well confirmed, medical ozone application in the form of the low-dose Accepted 10 May 2016
concept, is established and proven as a complementary medical method in the treatment of KEYWORDS
chronic inflammations or diseases associated with chronic inflammatory conditions. More than Evidence-Based Medicine;
11,000 systemic ozone treatments in the form of Major Ozone Autohemotherapy (MAH) in 577 Major Autohemotherapy;
patients and ≥ 47,000 Rectal Insufflations (RI) in 716 patients in various clinical studies are subjected
Downloaded by [Hacettepe University] at 13:51 27 June 2016

Ozone Medicine; Rectal

to critical clinical assessment and classification according to the criteria of evidence-based medicine Insufflation
(EBM). Statistically significant clinical and/or pharmacological improvements without side-effects or
adverse reactions are found in all studies; special attention is drawn to maintaining hygiene when
working with blood and to the use of ozone-resistent and biocompatible materials. On summarizing
the evidence classification under RCT + CT (Randomized Controlled Trials + Controlled Trials), i.e.,
Levels Ib and IIa, 12 studies with 657 ozone-treated patients are obtained for MAH and 6 studies with
227 patients for RI. As a result of the evidence here assessed, the two systemic ozone applications,
MAH and RI are part of evidence-based medicine. Both applications are effective, safe and economic.

Introduction adapted to the latest research results in 2012

(Viebahn-Hänsler, León Fernández, and Fahmy 2012).
To establish the best possible treatment strategy for the
In the meantime, still under controversial discussion
patients is the basic rational concept of evidence-based
and little noticed, the data for preclinical and clinical
medicine (EBM). Over and beyond its pharmacology
studies have completely changed: thousands of publica-
now based on well-founded and internationally published
tions on ozone therapy can be found in relevant medical
literature, the low-dose concept of medical ozone is
databanks, and the claim for classification and incorpora-
understood to be a complementary building block
tion in the context of Evidence-Based-Medicine is growing.
increasing the benefit/risk ratio, particularly in the treat-
This classification is here presented for the two most
ment of chronic inflammatory diseases or conditions
important systemic forms of application: major ozone
accompanied by chronic inflammation.
autohemotherapy (MAH) and rectal insufflation (RI).
For more than five decades now, good results in the
complementary therapy of inflammatory vascular
disease, rheumatoid arthritis or badly healing wounds
Clinical assessment
for example have been obtained worldwide; the appli-
cations have been optimized and standardized, making The integration of clinical expertise in the assessment and
ozone application in medicine an effective and low-risk classification of the data from clinical studies is accepted
treatment method. as a principle in evidence-based medicine. Scientific
Decades of experience, basic research on reactivity, publications in international journals, subjected to peer
concentration and the dose-dependent effects of medi- reviews and impact factor ranking, form the basis.
cal ozone, a considerable number of clinical studies and From the large number of classification modalities,
case studies have, finally, cumulated in the formulation those published by Cochrane Library (1992) and
of guidelines, now published in revised form and adapted according to the “Level of Evidence“ by the

CONTACT Renate Viebahn-Hänsler renateviebahn@t-online.de Nordring 8, Iffezheim/Baden-Baden D-76473, Germany.

Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/BOSE.
© 2016 International Ozone Association
 2 R. VIEBAHN-HÄNSLER ET AL.

Oxford Center for Evidence-Based Medicine (2009), 1.1 Major Ozone Autohemotherapy (MAH)
have been selected. See Table 1.
Angiopathia
The main prerequirements in assessing clinical data
Arterial circulatory disturbances
are (note: each prerequirement is discussed in detail in
Chronic inflammatory rheumatic disease
the paragraphs to follow this list):
Virus-conditioned diseases
Immune deficiency
(1) Guidelines with a clear concept of indications,
Complementary oncology
applications, concentrations, dosages and treat-
The standard concentrations and recommended
ment frequencies
doses are given in Table 2
(2) Standardized treatment procedures
(Beck, Wasser, and Viebahn-Haensler 1998).
(3) Knowledge concerning the pharmacology of
ozone in the corresponding indications 1.2 Rectal insufflation
(4) Reference substances for measurable success
control in addition to the clinical, indication- In addition to the indications cited for MAH, those
specific parameters. for RI also include local diseases, such as colitis, proctitis
or anal fissures. In this context see Table 3 (Beck,
(1) The Guidelines for the application of ozone in Wasser, and Viebahn-Haensler 1998), in which the
standard doses are also listed.
Downloaded by [Hacettepe University] at 13:51 27 June 2016

medicine define the indication range and the forms of

application as well as the concentrations and the dose
ranges (Viebahn-Hänsler, León Fernández, and Fahmy (2) Standardized treatment applications
2012).
Figures 1 and 2 give examples of proven and standar-
dized methods for carrying out systemic ozone
Indications administration.
As a complementary systemic use, these generally com-
(3) The pharmacology of systemic ozone application
prise chronic inflammatory diseases or inflammatory
symptoms.
Chronic inflammatory processes are always accompa-
nied by: high oxidative stress, reactive oxygen species, such
Table 1. Levels of evidence according to Cochrane Library 1992
based on Oxford 2009. as radical and nonradical oxidants, a suppressed antioxi-
Level Evidence-type dant capacity and immunologic disbalance, each of which
Ia At least 1 systematic review of high quality randomized cntrolled in turn promotes and maintains the inflammatory process.
studies (RCTs) At low doses, systemically applied ozone in the form
Ib At least 1 high-quality randomized controlled trial RCT
IIa At least 1 high-quality nonrandomized trial of MAH and RI acts as a bioregulator, such as schema-
IIb At least 1 high-quality trial without control group tically shown in Figure 3: as a reaction product from O3
IIIa More than 1 high-quality controlled case study
IIIb High quality noncontrolled case study and unsaturated fatty acids (isolated double bonds),
IV Expert opinion as clinical experience is concerned “ozone peroxides” induce a signal transduction via the

Table 2. MAH. Standard recommendation for MAH treatment (Beck, Wasser, and Viebahn-Haensler 1998) (has to be adapted to
indication and patient´s general condition).
50 ML OF BLOOD + 50 ML OZONE OXYGEN MIXTURE
(or 100 ml of ozone per 100 ml of blood)
Ozone concentration per ml of gas 10–20 µg/ml gas 30 µg/ml gas Recommended maximum 40 µg/ml gas
Biologically relevant concentration 10–20 µg/ml blood 30 µg/ml blood 40 µg/ml blood
Total ozone amount per 50 ml blood 500–1.000 µg per treatment 1.500 µg per treatment 2.000 µg per treatment

Table 3. RI. Indications and dosages for rectal ozone-insufflation.

Local effect Dosage
Ulcerous colitis Local: in ulcerous colitis, high O3/O2 concentrations (70-80–100 µg/ml) and small volumes (50 ml) are applied;
Proctitis, stages I and II on cessation of hemorrhage, this is reduced to 30–20 µg/ml, followed by systemic efficacy: 10–20 µg/ml,
Anal fistulae and fissures 150–300 ml volume.
Systemic effect Dosage
Indications cited for MAH Systemic: 10–25 µg ozone/ml oxygen gas mixture, volume 150–300 ml;
Hepatitis B and C for children: 10–20 µg/ml, volume 10–30 ml
For immunomodulation
complementary method in oncology
 OZONE: SCIENCE & ENGINEERING 3

monitoring oxidative stress parameters, specific antioxi-

dants and characteristic cytokines.
Figure 4 shows rheumatoid arthritis RA as an example
for the pharmacological effect of systemically administered
ozone (León Fernández 2015).

(4) Reference substances

On sorting through the large number of cell and animal

Figure 1. Major autohemotherapy standardized system accord-
ing to the Medical Device Directives 93/42 EC.
Downloaded by [Hacettepe University] at 13:51 27 June 2016
models as well as the clinical studies contributing to the
pharmacological understanding of medical ozone, the cri-
tical parameters shown in Table 4 are found to be easily
reproducible and usable as suitable reference substances in
daily practice (Figures 3 and 4).
One or the other reference substance is to be given
preference as indication demands; an example for this is
found with NO where inflammatory vascular disease is
concerned. In animal studies, the bioregulative effect of

(1) Ozone syringe (Polypropylene) low-dosed ozone in the organs can be directly monitored
(2) Bacterial filter (0.2 µm) on site, particularly in liver, kidney and spleen (Safwat, El-
(3) Vacuum bottle (glass) Sawalhi, and Mawsouf 2015).
(4) Transfusion set (polyethylene) A controlled clinical study in rheumatoid arthritis
RA depicts exemplarily this bioregulation (Figure 4):
the upregulation of antioxidants and decrease of oxida-
tive stress as a consequence after 20 systemic treatments
in the form of rectal insufflation. The antioxidants
SOD, CAT and GSH are upregulated; oxidative stress
decreases by downregulation of ROS: NO, AOPP, TH,
MDA. An immunomodulation has been measured as
downregulation of IL-1, IL-6 and TNF-α (not shown).
Ozone is generally administered as a complementary,
here in 30 patients in addition to Methotrexate (MTX)
as basic therapy, as compared to 30 patients in the
MTX control group (León Fernández 2015).

Material and methods

Figure 2. Set for rectal insufflation standardized system accord- Literature search: Methods
ing to the Medical Device Directives 93/42 EC.
Without temporal or other restrictions, the relevant
(1) Dosage ball (silicone) databanks, Medline, Pubmed and Cochrane as well as
(2) Storage bag “Ozone: Science and Engineering,” the scientific jour-
(3) Clamb nal of the International Ozone Association IOA, were
(4) One-way valves used for systematic data search.
(5) Connection line (PE) Keywords: 1. Ozone therapy, Major Autohemotherapy
(6) Catheter (PE) 2. Ozone therapy, Rectal Insufflation

oxidation of glutathion or cysteine residues and the

corresponding nuclear factors, resulting in a regulation
of the antioxidants via Nrf2 information, or an immu-
nomodulation via NFkB.
In addition to the indication-relevant clinical para-
meters, the course of treatment can be followed by
Exclusion criteria
For an EBM assessment of these two systemic med-
ical ozone applications, only clinical studies can be
used. For this reason, the following are excluded:
cell and animal studies and those taking other
 4 R. VIEBAHN-HÄNSLER ET AL.
Downloaded by [Hacettepe University] at 13:51 27 June 2016
Figure 3. Pharmacological effects of ozone: signal tranduction via glutathione or cysteine oxidation by “ozone peroxides,“ informa-
tion of nuclear factors and finally regulation of the response proteins such as antioxidants or cytokines.
application forms as their subject, such as Minor
Ozone Autohemotherapy, which induces a comple-
tely different active mechanism due to its intramus-
cular administration form.
Purely experimental ex vivo studies undertaken to
support ozone pharmacology or its nontoxicity also
fall under exclusion criteria. These include reviews
on the value and position of medical ozone
application.
Inclusion criteria
All data taking clinical studies and case studies on
major ozone autohemotherapy and rectal insuffla-
tion or a combination of both as their subjects
form the basis of this assessment.
Adverse events (side-effects) and adverse reac-
tions were searched for in all databanks, also with-
out any limitations as to time or content.
Results of the literature search
MAH
For major ozone autohemotherapy, 65 data were obtained
from the databases. After application of exclusion and
inclusion criteria, and double elimination, 21 clinical stu-
dies or case studies remained. All results are all listed in
Appendix Table 9, A/MAH 1.0; Appendix Table 10, B/
MAH 1.0 and evaluated in Appendix Tables 11–15, A/
MAH 1.1–1.5 and Appendix Table 16, B/MAH 1.1.
A total of 881 patients were treated, of which 577
received MAH, corresponding to over 11,207 ozone
treatments; 299 patients were used as control groups
(see Table 5).
RI
The literature search for rectal insufflation, resulted in 34
publications, listed in Appendix Table 17, A/RI 1.0 and
Appendix Table 18, B/RI 1.0, and B/RI 1.0, evaluated in
 OZONE: SCIENCE & ENGINEERING 5

(a) In the case of MAH, 2 references could be found with

180
indications of cautionary measures. These have been
160
assessed separately in the data analysis. In the same way,
140 two hints for mild irritation were discovered in rectal
120 insufflation, also analyzed and evaluated under the head-
100 ings “Data Analysis” and “Safety Aspects,“ which follow.
80
60
40 Data analysis and results
20
To obtain relevant and valuable results, all included pub-
0
lications were weighted according to the type of clinical
(b) SOD (u/mL/min) CAT (u/L/min) GSH (µM)
study and the number of patients (Appendix Tables 11–
60
15, A/ MAH 1.1–1.5 and Appendix Table 16, B/MAH
50 1.1, as well as Appendix Tables 19–20, A/RI 1.1–1.2 and
40 Appendix Table 21, B/RI 1.1) based on a quality score
30
according to (Steppan et al. 2010) (Table 6a).
With a ranking between 0.4 and 1.1, case studies,
Downloaded by [Hacettepe University] at 13:51 27 June 2016

20
clinical studies, noncontrolled and controlled studies
10 (CT) including randomized controlled clinical studies
0 (RCT) are comprised such as put together in Table 6b
NO (µM) AOPP (µM) TH (µM) MDA (µM) for MAH and 6c for RI.
ozone control

Figure 4. Reference substances to follow the treatment success
in patients with RA (rheumatod arthritis) Antioxidants (a) and
parameters of oxidative stress (b). Ozone group (n = 30): meth-
otrexate + ozone), control (n = 30): methotrexate.SOD: super-
oxide dismutase, CAT: catalase, GSH: reduced glutathione, NO:
nitrogen oxide, AOPP: advanced oxidation protein products, TH:
total hydroperoxides, MDA: malondialdehyde
Appendix Tables 19–20, A/Rectal 1.1–1.2 and Appendix
Table 21, B/RI 1.1; after double elimination as well as
applying exclusion and inclusion criteria, 13 clinical studies
and case studies for further evaluation remained. 716
patients out of 966 were assigned to rectal ozone applica-
tion with a total of more than 46,984 treatments (see
Table 5).
All treatments were found to be free of side-effects,
no adverse reactions occurred.
Major ozone autohemotherapy
Two randomized, controlled clinical studies with 208
patients and 97 ozone patients, and 10 controlled
studies with 260 patients out of 449 form the majority
of the evaluated data.
Any of the clinical studies showed a statistically
significant improvement in clinical parameters and/or
the characteristic reference substances, such as antiox-
idant status or oxidative stress. No adverse reactions
occurred; in all clinical studies as well as the case
reports (with a total of 577 patients in the ozone
groups), the high level of efficacy and safety of the
method are emphasized.
The fact that nonrandomized groups dominate is in
the nature of a complementary medical procedure; for
the most part, patients do not receive ozone therapy

Table 4. Reference substances during systemic ozone treatment.

Oxidative stress Antioxidant status Cytokins
TH total hydroperoxides Total SOD superoxide Interleukine IL-1, IL-6,
MDA malondialdehyde dismutase TNFα
NO nitrogen oxide GSH-reduced glutathion Tumor necrosis factor-α

Table 5. Results of data research.

Type of treatment Number of selected data Number of patients N1/N* Number of treatments Side effects reported Risk description irritations
MAH 21 of 65 577 /881 ≥ 11,207 none 2
Rectal Insufflation 13 of 34 716 /966 ≥ 46,984 none 2
*N1 /N: number of ozone treated patients (N1) in relation to the total number. N—N1 = number of patients as control
 6 R. VIEBAHN-HÄNSLER ET AL.

Table 6a. Quality evaluation score (based on Steppan et al. 2010). (1) Foglieni C., A. Fulgenzi, D. Belloni, C. Sciorati,
Study criteria Base score E. Ferrero, M. E. Ferrero. Ozonated autohe-
Randomized 0.9 motherapy: protection of kidneys from ischemia
Prospective 0.8
Case trial > 6 patients 0.7 in rats subjected to unilateral nephrectomy. BMC
Case trial ≤ 6 patients 0.6 Nephrology 12 p. 61/2011
Additional credits Comment: Incorrectly reported under “adverse
Control group  yes + 0.1
 no - 0.1 events”; the protective effect of oxidative pre-
Statistical analysis  yes + 0.1 conditioning by MAH in kidneys and liver is
 no - 0.1
described and this has been confirmed by León
et al. in different animal studies.
until conventional applications are no longer tolerated or (2) Oxygen Therapies. Cassileth 2009, Oncology
results are either absent or unsatisfactory; typically aris- (Willston Park, N.Y.) Vol: 23 (13); p 1182/
ing where chronic diseases are involved, such as virus 20091130
hepatitis in patients, in whom standard interferone ther- Comment: This involves a criticism of all oxygen
apy by itself had produced no improvement. This also therapy forms, including MAH: A warning is
applies for diabetic angiopathia in its advanced stages. issued against all clinics claiming to heal cancer.
When classified according to indications, the Complementary oncology is on the list of ozone
Downloaded by [Hacettepe University] at 13:51 27 June 2016

ozone groups in Table 7a break down into 206 indications, though here with the claim for a pro-
patients with vascular inflammatory diseases and tective effect against free radicals from chemother-
arterial circulatory disturbances, 203 patients with apy, and not as an anticarcinogenic therapy.
chronic hepatitis, and 122 patients with chronic
inflammation and immune deficiency. In addition, two references from literature with a
negative aspect are taken from
Appendix Table 12, A/MAH:
A22 A cluster of hepatitis C virus infections associated
Adverse events
with ozone enriched transfusion of autologous blood in
The data search yielded 2 adverse events: Rome, Italy.

Table 6b. MAH. Classification of the results of literature search.

Type of article Number of articles Number of patients Number of MAH treated patients Adverse events
RCT Randomized controlled trial 2 208 97 none
CT Controlled trial 10 449 260 none
T Noncontrolled trials 2 82 82 none
Controlled case studies 3 77 20 none
Case reports 4 14 14 none
Total number 21 830 473 none
Risk description 2 n.a. n. a. Hygiene;
Material.

Table 6c. RI. Summary of the literature search. Selected publications: 16 of 65.
Type of article No. of articles No. of patients No. of MAH treated patients Adverse events
RCT Randomized controlled trial 2 204 78 none
CT Controlled trial 4 273 149 none
T Noncontrolled trials 6 484 484 none
Case reports 1 5 5 none
Total number 13 966 716 none

Table 7a. MAH. Data analysis in dependence on the indication.

Indication Number of MAH treated patients Results
Angiopathia diabetica, N = 206 Statistically significant improvement of clinical and biochemical parameters,
retinopathia, no side effects
circulatory disorders
Chronic hepatitis N = 203 Statistically significant improvement of clinical and biochemical parameters,
no side effects
Chronic inflammation, N = 122 Statistically significant improvement of clinical and biochemical parameters,
immunodisbalance no side effects
MAH is efficient, safe, no side effects reported

During blood treatment there is the danger of
transmitting an infection when the rules of hygiene
are not adhered to:
Adherence to hygiene regulations particularly when
working with blood must be maintained at all times.
Reference 22 in Appendix Table 12, A/MAH 1.2 reports
retrospectively on possible transmissions of hepatitis.
Although the path of infection could not be clarified
without doubt, attention must nevertheless be drawn to
Hygiene Guidelines in particular, as the Guidelines
on Ozone Therapy clearly document these: the use of
disposible material and utilities including bacterial filters.
A39 Combination of LC-MS and GC-MS-based
metabolomics to study the effect of ozonated autohe-
motherapy on human blood.
Liquid and gas chromatographic investigations in A39
Appendix Table 13, A/MAH 1.3 demonstrate the release
Downloaded by [Hacettepe University] at 13:51 27 June 2016
of plasticizers. No damage to patients occurred.
Conclusion: Only ozone-resistant and pharmacologically
indifferent materials must be used. Blood bags made of PVC
capable of coming into contact with ozone when preparing
and carrying out MAH do not belong here.
Safety Aspects
In Appendix Tables 11–15, A/MAH 1.1–1.5, a total
of 19 references were subjected to a critical analysis,
in Appendix Table 16, B/MAH 1.1 two further data
sets, with a total of 881 patients, of which 577 (57.0
%) were in the verum groups. This correponds to at
least 11,207 MAH.
The number of treatments per patient varies greatly
according to indication and patient, and can be
between 1 and >30 treatments, e.g., 1 MAH for acute
stroke (40 in Appendix Table 14, A/MAH 1.4), or 32
MAH in chronic hepatitis C; some of the patients were
treated over 6 months (B5 in Appendix Table 16, B/
MAH 1.1). The citing of mean values is therefore of
little value.
In none of the 577 ozone-treated patients with more
than 11,207 applications in the form of MAH a system-
or product-related incident or an adverse effect has
been described (see Tables 5 and 6b).
Confirmation of safety in the context of negative
hematological or biochemical changes is supported
by the following data from literature: 6, 8, 10, 17,
39, 42 from Appendix Tables 11–14, A/MAH 1.1–1.4.
The concentration-dependent influence in all hema-
tologically relevant parameters can be cited as an
example (6 in Appendix Table 11, A/MAH 1.1):
even at the highest concentrations available up to
100 µg/ml, no undesirable or negative effects whatos-
ever occurred.
OZONE: SCIENCE & ENGINEERING 7
Results of the safety assessment
Major Ozone Autohemotherapy MAH is a low-risk
treatment method.
The benefit/risk ratio, with only one described risk
when working with blood, is by far on the benefit side
(see Table 5).
Even if nonadherence to hygiene rules during treat-
ment (intramuscular + MAH) could be claimed for all
of the 3 hepatitis C patients in A22, a benefit/risk
relation of 577: 3 patients or a risk of 0.52% would
here apply, and much less when seen in relation to the
total number of treatments.
Note: Hygiene guidelines, such as described for every
kind of work with blood in laboratory, clinic and
practice, must be adhered to at all times; the relevant
measures to be taken as well as the materials to be used
are described in the Guidelines and apply for all users.
Evidence assessment
Finally, on application of the evidence classification system
according to Cochrane Library (1992) based in turn on the
system described by the Oxford Center for Evidence-
Based-Medicine (2009) (Table 1), all assessed data listed
in Appendix Tables 11–15 (A) and Appendix Table 16 (B)
are assigned to the evidence level. Preclinical studies car-
ried out for safety purposes are correspondingly described.
Table 8a orders the publications according to
evidence level: In total, two controlled randomized
clinical studies (N = 97) have evidence level Ib, 10
controlled studies IIa (N = 261), 3 clinical studies
with nontreated control groups (N = 192) level IIb. 2
controlled case studies with 14/19 patients and 3 case
reports (N = 13) can be assigned to level III.
Conclusion: Major Ozone Autohemotherapy is within
the clinical range of Evidence-Based Medicine.
Rectal insufflation
For assessment and evidence assignment of rectal insuffla-
tion as systemic ozone treatment (Appendix Table 17, A/
RI 1.0 and Appendix Table 18, B/RI 1.0), 12 clinical studies
and 1 case report could be identified; of these, 2 rando-
mized controlled clinical studies with 78 ozone patients
out of 204, four controlled studies with 149/273 patients,
six studies without a control group comprising 484, as well
as one individual case study with 5 patients (see Table 6c).
Statistically significant improvements in clinical
parameters and/or the characteristic reference sub-
stances, such as antioxidant status or oxidative stress,
were calculated in all studies. No adverse reactions
occurred; slight irritations in the form of transient
 8 R. VIEBAHN-HÄNSLER ET AL.

Table 7b. RI. Data analysis in dependence on the indication.

Indication Number of RI-treated patients Results
Angiopathia, N = 155 Statistically significant improvement of clinical and biochemical parameters,
Retinopathia, no side effects
circulatory disorders
Chronic hepatitis N = 150 Statistically significant improvement of clinical and biochemical parameters,
no side effects
Chronic inflammation, N = 307 Statistically significant improvement of clinical and biochemical parameters,
immunodisbalance, no side effects. 2 minor irritations.
chronic inflammatory bowel disease
Chronic rheumatoid inflammation, N = 78 Statistically significant improvement of clinical and biochemical parameters,
chronic pain no side effects.
The rectal application of ozone/oxygen mixtures is efficient, safe, no side effects reported.

Table 8a. MAH. Final evaluation of evidence.

Evidence classification No. of articles No. of MAH patients N1/N* Evidence grade Article No.
RCT Randomized controlled trial 2 97/208 Ib A/MAH:
38,44
CT Controlled trial 10 261/449 IIa A/MAH:
13,14, 15, 16, 19, 24, 31, 37, 40, 46,
T Noncontrolled trials 3 192/192 IIb A/MAH:
Downloaded by [Hacettepe University] at 13:51 27 June 2016

5, 45,
B/MAH: B5
Controlled case studies 2 14/19 IIIa A/MAH
41, 47
Case reports 3 13/13 IIIb A/MAH
10, 26, 43,
*N1 /N: No. of ozone MAH-treated patients (N1) in relation to total number. N—N1 = No. of patients as control

flatulence immediately after rectal insufflation are
described in two cases. In all studies, with a total of
716 patients in the ozone groups and more than 46,984
treatments, attention is drawn to the high level of
efficacy and safety of the method.
Table 7b provides information on the basic indica-
tions: Angiopathia and retinopathia in 155 patients,
chronic hepatitis in 150, chronic inflammatory intestinal
diseases and immune disbalance in 307, and chronic
inflammatory rheumatic diseases in 78 patients.
Adverse events
The data search yielded 0 “adverse events.”
In two cases (Appendix Tables 19–20, A/RI 1.1–1.2),
slight transient irritations are listed, but not classified as
adverse reactions or safety-relevant:
6 in Appendix Table 19, A/RI 1.1: ND = ME23046293
MEDLINE (ME60)
Ozone therapy as add-on treatment in fibromyalgia
management by rectal insufflation: in open-label pilot
study. Journal of Alternative and Complementary
Medicine (New York, NY) 19 (3):238–42/201303/
As slight irritation, transitory flatulence after rectal
ozone administration is cited, however, without any
influence on the treatment results, i.e., a statistically
significant improvement in clinical findings. The
method has proven itself to be simple and safe to apply.
The volume of 200 ml ozone-oxygen mixture could
hardly be the cause. However, the ozone concentration in
RI is, at 40 µg/ml, in the upper range for this application
and the probable reason for the irritation; the Guidelines
recommend ≤ 25 µg/ml for chronic inflammatory diseases.
Does ozone alleviate AIDS diarrhea? Journal of
Clinical Gastroenterology 17 (2):142–5/199309/
21 in Appendix Table 20, A/RI 1.2:
ND = ME08409316 MEDLINE (ME60)
Mild, short-term irritation during ozone insufflation.
Systemically, no adverse reactions; treatment is
described as safe, simple and effective: treatment of
diarrhea in 5 HIV patients with full-blown AIDS,
successful in 4 patients.
Safety aspects
In total, 16 data sets comprising 12 clinical studies and
1 case report involving 966 patients, of which 716 were
in the verum group corresponding to 74.1% were sub-
jected to critical evaluation. This corresponds to more
than 46,984 rectal ozone applications.
Here, too, mean values per patient would not be of
any value; according to indication, the number of ozone
applications varies between 1 and 40 treatments per year,
such as for example where long-term studies involving
hepatitis C or retinitis pigmentosa are concerned.
 OZONE: SCIENCE & ENGINEERING 9

In 716 patients and ≥ 46,984 ozone insufflations no
system or product-related incidents or adverse reac-
tions has been described; in two cases, there was slight
transient flatulence immediately after rectal ozone
insufflation (Table 5).
Results of safety assessment
Rectal ozone insufflation is a low-risk treatment
method, described as being effective, safe and simple.
With only a few slight and transient irritations in the
form of flatulence, the benefit/risk ratio is by far on the
benefit side (see Table 7b).
Evaluation of evidence
As described previously for the reinfusion of ozonized
Downloaded by [Hacettepe University] at 13:51 27 June 2016
1.1–1.2 and Appendix Table 21, B/RI 1.1, quality features
and evidence classes are assigned to the individual publica-
tions; preclinical studies only carried out for safety pur-
poses are correspondingly noted as such.
In summarized form, Table 8b shows 2 controlled, ran-
domized clinical studies with N = 78 in the verum group
corresponding to evidence level Ib, four clinical studies with
control group (N = 149 verum group) at evidence level IIa,
and six studies with 484 patients without control group at
evidence level IIb. The latter includes, among others, one
hepatitis C study and the treatment of radiation proctitis, in
which no control groups were available.
Based on this evaluation of evidence, Rectal Ozone
Insufflation is within the clinical range of Evidence-
Based Medicine.

Discussion and conclusions

blood, the evidence assessment criteria are based on the
classification system according to Oxford Center for The assignment of therapies, therapeutic applications
Evidence-Based Medicine (2009), adapted as per and diagnostic procedures to categories of evidence-
Cochrane Library 1992. In Appendix Tables 19–20, A/RI based medicine is mostly taken as a condition for cost

DATA SEARCH INCLUSION EVIDENCE

not limited as to time
MAH CLASSIFICATION
or subject
MAH: Ib + Iia
21 of 65 data
KEY WORDS 2 RCT: 97 patients,
Patients:
OZONE > 2,000 treatments
577 of 881
THERAPY + 10 CT: 261 patients,
Treatments:
> 11,200 > 6,200 treatments
1. AUTO
HEMOTHERAPY
MAH

2. RECTAL INCLUSION EVIDENCE

INSUFFLATION RI CLASSIFICATION
RI RI: Ib + Iia
13 of 34 data
DATA BASES Patients: 2 RCT: 78 patients,
PUBMED, MEDLINE 716 of 966 > 1,560 treatments
TAYLOR & FRANCIS 4 CT: 149 patients,
COCHRANE
Treatments:
> 36,730 treatments
ECOMED > 46,900

Figure 5. Results of data search and evaluation. MAH: major auto hemotherapy, RI: rectal insufflation RCT: randomized, controlled
trial, CT: controlled trial.

Table 8b. RI. Final evaluation of evidence.

Evidence classification No. of articles No. of RI patients/treatments Evidence grade Article No.
RCT Randomized controlled trial 2 78 /1560 Ib A/RI 8, 14
CT Controlled trial 4 149 /36730 IIa A/RI 10, 16
B/RI 5, 10
T Noncontrolled trials 6 484 /8694 IIb A/RI 5, 6, 25
B/RI 2, 4, 7
Controlled case studies IIIa
Case reports 1 5 IIIb A/RI 21
 10 R. VIEBAHN-HÄNSLER ET AL.
refunding by the health insurances or for inclusion
in Best Practice Guidelines (treatment concepts) for
general or special diseases.
Complementary medical procedures, which are always
and only applied as additives to conventional therapy
concepts are, as a rule, rarely included—and this even
although they represent low-price forms of medication,
which—seen for example in the case of ozone therapy for
rheumatoid arthritis (Figures 4a and 4b)—are frequently
found to have synergistic effects.
Here, based on a comprehensive literature search
(overview in Figure 5. Results of data search and evalua-
tion), the evidence assessments of the systemic ozone
treatment in the form of Major Autohemotherapy and
Rectal Insufflation is presented, both proven over dec-
ades as highly effective applications of medical ozone in
a complementary approach.
Downloaded by [Hacettepe University] at 13:51 27 June 2016
According to strict exclusion and inclusion criteria,
quality assessment has been carried out in 21 of 65 data
sets for MAH and in 13 of 34 for RI and assigned
according to the EBM classification in Table 1.
In the case of MAH, the majority of the clinical
studies refer to evidence level Ib and IIa, 12 controlled
clinical studies (CT), 2 of them randomized, compris-
ing 357 ozone patients.
For rectal administration, there were 6 controlled (Ib
and IIa) studies, 2 randomized, with 227 ozone patients,
6 studies without a control group comprising 484 ozone
patients and evidence level IIb, see Tables 8a and 8b.
The indications agree with the classic indications of
ozone therapy, as a rule associated with a chronic inflam-
matory process; the type of application also corresponds
to the classic and standardized application forms.
As classified according to indication fields, Table 7b
comprises the results for MAH and 7c those for RI: all
studies show statistically significant clinical and/or
pharmacological improvements, without adverse effects
or adverse reactions.
Both therapy forms were assessed as being effective and
safe in application, MAH in 577 patients of every age and
with the classic ozone indications at ≥ 11,207 applications;
RI in 716 patients and ≥ 46,984 applications.
Remarks on hygiene when working with blood are
strictly adhered to, all used materials must be ozone-
resistant and biocompatible; studies cited in two refer-
ences clearly point this out: See 22 in Appendix Table
12, A/MAH 1.2 and 39 in Appendix Table 13, A/MAH
1.3, which are discussed under “adverse events.” When
summarizing the evidence classification under RCT and
CT, i.e., levels Ib and IIa, 12 studies with 357 patients
are obtained for MAH, 6 studies with 227 patients
for RI.
As a result of this evidence assessment, the systemic
ozone applications Major Autohemotherapy and Rectal
Insufflation belong to Evidence-Based Medicine.
References
Beck, E. G., G. H. Wasser, and R. Viebahn-Haensler.
1998. “Ozontherapie in Wissenschaft Und Empirie.”
Komplement Med 5:61–75.
Cochrane Library. 1992. Evidenz Klassiifizierungssysteme.
Agency for Health Care Policy and Research, Department
of Health and Human Services. Acute pain management:
operative or medical procedures and trauma. Clinical prac-
tice guideline no. 1. AHCPR Publication 92–0032. Rockville,
MD, USA: AHCPR; 100–107 http://www.cochrane.de
León Fernández, O. S. 2015. “Targets of Medical Ozone in
Rheumatoid Arthritis. How Do They Impact in the
Clinical Scenery?“ Paper presented at the 22nd Ozone
World Congress of the International Ozone Association,
Barcelona, Spain, June 28–July 3.
Oxford Center for Evidence-Based Medicine. 2009. OCEBM
Levels of Evidence Working Group*. The Oxford 2011
Levels of Evidence. Oxford Centre for Evidence-Based
Medicine. http://www.cebm.net/index.aspx?o=5653
*OCEBM Table of Evidence Working Group = Jeremy
Howick, Iain Chalmers (James Lind Library), Paul
Glasziou, Trish Greenhalgh, Carl Heneghan, Alessandro
Liberati, Ivan Moschetti, Bob Phillips, Hazel Thornton,
Olive Goddard and Mary Hodgkinson.
Safwat, M., M. El-Sawalhi, and N. S. A. Mawsouf. 2015. “The
Role of Ozone in Ameliorating Oxidative Stress Associated
with Ageing in Rat Liver, Kidney and Blood.” Paper pre-
sented at the 22nd Ozone World Congress of the
International Ozone Association, Barcelona, Spain, June
28–July 3.
Steppan, J., T. Meaders, M. Muto, and K. Murphy. 2010. “A
Metaanalysis of the Effectiveness and Safety of Ozone
Treatments for Herniated Lumbar Discs.” Journal of
Vascular and Interventional Radiology 21 (4):534–48.
doi:10.1016/j.jvir.2009.12.393.
Viebahn-Hänsler, R., O. S. León Fernández, and Z. Fahmy.
2012. “Ozone in Medicine: The Low-Dose Ozone
Concept. Guidelines and Treatment Strategies.” Ozone:
Science & Engineering 34 (6):408–24. doi:10.1080/
01919512.2012.717847.
 OZONE: SCIENCE & ENGINEERING 11

Appendix

Table 9. A/MAH 1.0. Result of literature search MAH Medline (2015-02-09; 06:50 p.m.).
DIMDI -Medline Direct 09.02.15 18:50
1. Studies on the biological effects of ozone: 2. Induction of tumor necrosis factor (TNF-alpha) on human leucocytes.
ND = ME01768744 MEDLINE (ME60)
2. Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis.
ND = ME01435389 MEDLINE (ME60)
3. Studies on the biological effects of ozone: 3. An attempt to define conditions for optimal induction of cytokines.
ND = ME08324077 MEDLINE (ME60)
4. Studies on the biological effects of ozone: 6. Production of transforming growth factor 1 by human blood after ozone treatment.
ND = ME07660851 MEDLINE (ME60)
5. Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy.
ND = ME07635353 MEDLINE (ME60)
6. Susceptibilities of plasma antioxidants and erythrocyte constituents to low levels of ozone.
ND = ME10069448 MEDLINE (ME60)
7. Labor de la enfermera en la aplicación de la ozonoterapia en retinosis pigmentaria. Enero-mayo, 1996. -[The nurse’s work in the application of ozone
therapy in retinitis pigmentosa. January–May 1996].
ND = ME09934231 MEDLINE (ME60)
8. Studies on the biological effects of ozone: 7. Generation of reactive oxygen species (ROS) after exposure of human blood to ozone.
ND = ME09795834 MEDLINE (ME60)
9. Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells.
ND = ME11213910 MEDLINE (ME60)
10. Extracorporeal blood oxygenation and ozonation (EBOO) in man. preliminary report.
Downloaded by [Hacettepe University] at 13:51 27 June 2016

ND = ME10741810 MEDLINE (ME60)

11. Effect of ozone on red blood cell enzymes and intermediates.
ND = ME10692679 MEDLINE (ME60)
12. Effect of ozone on neutrophil function in vitro.
ND = ME11683785 MEDLINE (ME60)
13. Beneficial clinical effects of ozonated autohemotherapy in chronically dialysed patients with atherosclerotic ischemia of the lower limbs–pilot study.
ND = ME11256512 MEDLINE (ME60)
14. The influence of ozonated autohemotherapy on oxidative stress in hemodialyzed patients with atherosclerotic ischemia of lower limbs.
ND = ME12757028 MEDLINE (ME60)
15. No effects of ozonated autohemotherapy on inflammation response in hemodialyzed patients.
ND = ME15770057 MEDLINE (ME60)
16. Natural killer cell activity unaffected by ozonated autohemotherapy in patients with end-stage renal disease on maintenance renal replacement
therapy.
ND = ME15521216 MEDLINE (ME60)
17. Rational bases for using oxygen-ozonetherapy as a biological response modifier in sickle cell anemia and beta-thalassemia: a therapeutic perspective.
ND = ME15323359 MEDLINE (ME60)
18. Fistula function and dialysis adequacy during ozonotherapy in chronically hemodialyzed patients.
ND = ME15156869 MEDLINE (ME60)
19. Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study.
ND = ME14984181 MEDLINE (ME60)
0,00
20. Ozonated autohemotherapy in patients on maintenance hemodialysis: influence on lipid profile and endothelium.
ND = ME14961966 MEDLINE (ME60)
21. Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease.
ND = ME16288443 MEDLINE (ME60)
22. A cluster of hepatitis C virus infections associated with ozone-enriched transfusion of autologous blood in Rome, Italy.
ND = ME16209382 MEDLINE (ME60)
23. Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy.
ND = ME16156950 MEDLINE (ME60)
24. Ozone therapy effects on biomarkers and lung function in asthma.
ND = ME16099337 MEDLINE (ME60)
25. Can the combination of localized “proliferative therapy” with “minor ozonated autohemotherapy” restore the natural healing process?
ND = ME15951134 MEDLINE (ME60)
26. Major ozonated autohemotherapy in chronic limb ischemia with ulcerations.
ND = ME15865505 MEDLINE (ME60)
27. Restoration of normoxia by ozone therapy may control neoplastic growth: a review and a working hypothesis.
ND = ME15865491 MEDLINE (ME60)
28. Blood coagulation unaffected by ozonated autohemotherapy in patients on maintenance hemodialysis.
ND = ME17045123 MEDLINE (ME60)
29. Oxygen therapies.
ND = ME20043470 MEDLINE (ME60)
30. May oxygen-ozone therapy improves cardiovascular disorders?
ND = ME19519366 MEDLINE (ME60)
31. Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis.
ND = ME21034619 MEDLINE (ME60)
32. Ozone therapy: A clinical review.
ND = ME22470237 MEDLINE (ME60)
(Continued )
 12 R. VIEBAHN-HÄNSLER ET AL.

Table 9. (Continued).
33. Ozonated autohemotherapy: protection of kidneys from ischemia in rats subjected to unilateral nephrectomy.
ND = ME22081953 MEDLINE (ME60)
34. Adjuvant combined ozone therapy for extensive wound over tibia.
ND = ME21772635 MEDLINE (ME60)
35. Ozone acting on human blood yields a hormetic dose-response relationship.
ND = ME21575276 MEDLINE (ME60)
36. Ozone: a new therapeutic agent in vascular diseases.
ND = ME21446774 MEDLINE (ME60)
37. Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C.
ND = ME21417811 MEDLINE (ME60)
38. Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study.
ND = ME23275905 MEDLINE (ME60)
39. Combination of LC-MS-and GC-MS-based metabolomics to study the effect of ozonated autohemotherapy on human blood.
ND = ME23148940 MEDLINE (ME60)
40. Major ozonated autohemotherapy promotes the recovery of upper limb motor function in patients with acute cerebral infarction.
ND = ME25206688 MEDLINE (ME60)
41. Time and time-frequency analysis of near-infrared signals for the assessment of ozone autohemotherapy long-term effects in multiple sclerosis.
ND = ME24111149 MEDLINE (ME60)
42. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells.
ND = ME23253326 MEDLINE (ME60)
43. Long-term improvement in refractory headache following ozone therapy.
ND = ME23215625 MEDLINE (ME60)
44. The evaluation of ozone and betahistine in the treatment of tinnitus.
ND = ME23100082 MEDLINE (ME60)
45. [Dynamics of local expression of connexin-43 and basic fibroblast growth factor receptors in patients with skin and soft-tissue infections against the
Downloaded by [Hacettepe University] at 13:51 27 June 2016

background of diabetes mellitus type II].

ND = ME25552106 MEDLINE (ME60)
46. Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.
ND = ME25280029 MEDLINE (ME60)
47. Efficacy and safety of ozonated autohemotherapy in patients with hyperuricemia and gout: A phase I pilot study.
ND = ME25289033 MEDLINE (ME60)
48. [Prolonged epidural analgesia and ozonated autohemotherapy in complex surgical treatment at patients with thromboangiitis obliterans and critical
limb ischemia].
ND = ME25272682 MEDLINE (ME60)
49. Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result.
ND = ME25218903 MEDLINE (ME60)
50. Does ozone autohemotherapy have positive effect on neurologic recovery in spontaneous spinal epidural hematoma?
ND = ME24602896 MEDLINE (ME60)
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

Table 10. B/MAH 1.0. Literature search in “Taylor & Francis”: Ozone: Science & Engineering (2015-05-22; 03:01p.m.).
1 Viebahn-Hänsler, R., O. S. León Fernández, and Z. Fahmy. 2012.
“Ozone in Medicine: The Low-Dose Ozone Concept.
Guidelines and Treatment Strategies.”
Ozone: Science & Engineering 34:408–424.
2 Díaz-Soto, M. T., A. F. Pérez, J. D. Vaillant, A. Mallok, R. Viebahn-Haensler, S. Menéndez Cepero, and O. S. León Fernández. 2012.
“Ozone Oxidative Postconditioning protects against the injury associated to Alcohol Withdrawal Syndrome in Rats.”
Ozone Science & Engineering 34:425–431.
3 Díaz-Soto, M. Teresa, A. Fraga Pérez, J. Dranguet Vaillant, Mallok, A., R. Viebahn-Haensler, S. Menéndez Cepero, and O. S. León Fernández. 2012.
“Ozone Therapy Ameliorates Nervous System Disorders and Plasmatic Oxidative Stress in Patients During Ethanol Withdrawal-A Pilot Study.”
Ozone: Science & Engineering 34:432–437.
4 Fathi, A.M., M.N. Mawsouf, and R. Viebahn-Hänsler. 2012. “Ozone Therapy in Diabetic Foot and Chronic, Nonhealing Wounds.” Ozone Science & Engineering 34:438–450.
5 Mawsouf, M.N., T.T. Tanbouli, and R. Viebahn-Haensler. 2012.
“Ozone Therapy in Patients with viral hepatitis C—Ten Years Experience.“
Ozone: Science & Engineering 34:425–431.
6 Alexandre, A, L. Corò, R. Paradiso, R. Dall’Aglio, A.M. Alexandre, F.
Fraschini, and P.G. Spaggiari. 2012.
“Symptomatic Spinal Degenerative Pathologies. Clinical Results with the Application of Conservative Biochemical Treatments.”
Ozone: Science & Engineering 34:459–468.
7 Calunga, J.L., S.Menendez, R. Léon, S. Chang, D. Guanche, A. Balbín, J. Zayas, and P. Gará. 2012. “Application of Ozone Therapy in Patients with Knee Osteoarthrosis.” Ozone: Science & Engineering 34:469–475.
8 Copello, M., S. Menéndez, and F. Hernández. 2012.
“Ozone Therapy in Retinitis Pigmentosa Patients: Clinical Evolution and Oxidative Stress Behavior in Retinitis Pigmentosa Patients Treated with Ozone Therapy During 20 Years.” Ozone: Science & Engineering
34:475-483.
9 Zimmermann, D., T. Waltimo, and A. Filippi. 2012.
“Ozonized Water in Dental Traumatology—
A Preliminary Study on the Treatment of Avulsed Teeth, in vitro.”
Ozone: Science & Engineering 34:484-488.
10 See 1. Double
11 Bocci, V.C., G. Borelli, A. Corradeschi, G. Diadori, G. Fanetti, and G. Valacchi. 2001. “Ozone in Medicine.” Ozone: Science & Engineering 23:207–217.
12 Rilling, S. 1985. “The Basic Clinical Application of Ozone Therapy.”
Ozone: Science & Engineering 7:259–274.
13 Washüttl, J., R. Viebahn, I. Steiner, and F. Gstirner. 1989. “Immunological Examinations in Patients with Chronic Conditions under Administration of Ozone/Oxygen Mixtures.” Ozone: Science & Engineering 11:411–
417.
14 Mawsouf M.N., T.T. Tanbouli, and R. Viebahn-Haensler. 2012.
“Ozone Therapy in Patients with Viral Hepatitis C—Ten Years Experience.“
Ozone: Science & Engineering 34:425–431.
15 Bocci, V., and N. Di Paolo. 2010. “Oxygenation-Ozonization of Blood During Extracorporeal Circulation (EBOO) Part III: A New Medical Approach.”
Ozone: Science & Engineering 26:195–205.
16 Alexandre, A., L. Corò, R. Paradiso, R. Dall’Aglio, A.M. Alexandre, F.
Fraschini, and P.G. Spaggiari. 2012. “Symptomatic Spinal Degenerative Pathologies. Clinical Results with the Application of Conservative Biochemical Treatments.” Ozone: Science & Engineering 34:459–468.
OZONE: SCIENCE & ENGINEERING
13
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

14

Table 11. A/MAH 1.1. Result and assessment of literature search in MAH treatment (Medline).
Results Statistics
No. of Adverse events Quality ranking
patients N1 O3 conc. in µg/mL No. of Therapeutically Relevant /Safety Level of
Nr. Source Type Indication /N* Age MAH treatments Clinical Data Parameters statement evidence
5 Decrease of blood cholesterol and stimulation Clinical study, Ischemic 22/22 50 µg/mL 15 sessions per RBC antioxidants G6PDH, No adverse 0.8 IIb
of antioxidative response in cardiopathy no control cardiopathy 46–76 yrs patient, in total: 330 MAH GSH. LPO in plasma event Safe
R. VIEBAHN-HÄNSLER ET AL.

patients treated with endovenous ozone p < 0.05

therapy.
Free Radical Biology & Medicine 19(1):115–9/
199507/
ND = ME07635353 MEDLINE (ME60)
6 Susceptibilities of plasma antioxidants and Safety n.a n.a. 40 µg/mL; 20–100 µg/mL GSH p < 0.05 n.a Preclinical trial
erythrocyte constituents to low levels of pharmacol.
ozone. effect
Haematologia29 (3):229–39/1998/ blood
ND = ME10069448 MEDLINE (ME60)
8 Studies on the biological effects of ozone: 7. Safety n.a. n.a. 50–100 µg/mL blood ITNF-α, IL-1, n.a. Preclinical trial
Generation of reactive oxygen species (ROS) pharmacol. γ-IFN
after exposure of human Blood to ozone. effect p < 0.05
Journal of Biological Regulators and
Homeostatic Agents 12 (3): 67–75/1998 Jul–
Sep/
ND = ME09795834 MEDLINE (ME60)
10 Extracorporeal blood oxygenation and Case study n.a. 6 0.5–10 µg/mL Clinical improve- No adverse 0.4
ozonation (EBOO) in man. preliminary report. clinical > 80 yrs ment event IIIb
validation Safe
International Journal of Artificial Organs
VOL:23(2); p.131-41/200002/
ND = ME10741810 MEDLINE (ME60)
13 Beneficial clinical effects of ozonated Clinical Peripheral 12/12 34,4 µg/mL Clinical improve- No adverse 1.0
autohemotherapy in chronically dialysed study, vascular Elderly 14 MAH/pat. ment in walking event IIa
patients with atherosclerotic ischemia of the control 5/7 disease, In total:168 distance) Safe
lower limbs–pilot study. hemodial. dialyzed p ≤ 0,01
The International journal of artificial organs /intraperit. kidney failure
VOL:24(2); p.79-82/200102/ dialyzed
ND = ME11256512 MEDLINE (ME60)
14 The influence of ozonated autohemotherapy Controlled Hemodialyzed, 12 50 µg/mL Clinical improve- GSH in RBC No adverse 1.0
on oxidative stress in hemodialyzed patients clinical study kidney failure Elderly 9 MAH/pat ment p < 0.05 event IIa
with atherosclerotic ischemia of lower limbs. In total: 108 Safe
The International journal of artificial organs
VOL:26(4); p.297-303/200304/
ND = ME12757028 MEDLINE (ME60)
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

Table 12. A/MAH 1.2. Result and assessment of literature search in MAH treatment (Medline).
No. of O3 conc. in Results Statistics
patients µg/mL
N1 /N* No. of MAH Therapeutically Relevant Adverse events Quality ranking
Nr. Source Type Indication Age treatments Clinical Data Parameters /Safety statement Level of evidence
15 No effects of ozonated autohemotherapy on Controlled clinical trial, cross Hemodialyzed, 12/12 50 µg/mL Clinical C-reactive protein, IL-6 No adverse event 1.0
inflammation response in hemodialyzed over study kidney failure Eldery 9 MAH/pat. improve- No inflammatory Safe IIa
patients. In total: 108 ment response
Mediators of inflammation VOL:13(5-6); p.377-
80/200412/
ND = ME15770057 MEDLINE (ME60)
16 Natural killer cell activity unaffected by Controlled clinical trial, cross- Hemodialyzed, 12/12 50 µg/mL Clinical No statistical increase of n.a. 1.0
ozonated autohemotherapy in patients with over study kidney failure 64.8 ± 7.6 9 MAH/pat. improve- natural killer cells No adverse event IIa
end-stage renal disease on maintenance renal In total: 108 ment Safe
replacement therapy.
The International journal of artificial organs
VOL:27(9); p.766-71/200409/
ND = ME15521216 MEDLINE (ME60)
17 Rational bases for using oxygen-ozonetherapy Therapeutic perspective n.a. n.a. IV
as a biological response modifier in sickle cell
anemia and beta-thalassemia: a therapeutic
perspective.
Journal of biological regulators and
homeostatic agents VOL:18(1); p.38-44/2004
Jan-Mar/
ND = ME15323359 MEDLINE (ME60)
19 Clinical efficacy of ozonated Controlled clinical trial, cross Peripheral 10 50 µg/mL Clinical P < 0.01 No adverse event 1.0
autohemotherapy in hemodialyzed patients over study vascular disease Elderly improve- Safe IIa
with intermittent claudication: an oxygen- ment
controlled study.
The International journal of artificial organs
VOL:27(1); p.29-34/200401/
ND = ME14984181 MEDLINE (ME60
22 A cluster of hepatitis C virus infections Retrospective cohort study as n.a. 3/31 n.a. n.a. n.a. Suspected adverse
associated with ozone-enriched transfusion of regards hepatitis C effect
autologous blood in Rome, Italy. transmission
Infection control and hospital epidemiology
VOL:26(9); p.762-7/200509/
ND = ME16209382 MEDLINE (ME60)
24 Ozone therapy effects on biomarkers and Controlled clinical study Asthma 35/113 20 µg/mL Clinical IgE, HLA-DR No adverse event 1.0
lung function in asthma. 3 groups 41/113 40 µg/mL improve- p < 0.05 Safe IIa
Archives of medical research VOL:36(5); p.549- 15–50 15 MAH/pat. ment
54/2005 Sep-Oct/ 3 cycles
ND = ME16099337 MEDLINE (ME60) In total: 3420
OZONE: SCIENCE & ENGINEERING
15
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

16

Table 13. A/MAH 1.3. Result and assessment of literature search in MAH treatment (Medline).
No. of O3 conc. in Results Statistics
patients µg/mL Weighting
N1 /N* No. of MAH Clinical Adverse events /Safety level of
Nr. Source Type Indication age treatments Data Therapeutically relevant parameters statement evidence
R. VIEBAHN-HÄNSLER ET AL.

26 Major ozonated autohemotherapy in chronic Case reports Diabetes II, 2/2 24 MAH/pat Clinical No adverse event 0.4
limb ischemia with ulcerations. vascular ischemia Eldery In total: 48 improve- Safe IIIb
Journal of alternative and complementary ment
medicine (New York, N.Y.) VOL:11(2); p.363-7/
200504/
ND = ME15865505 MEDLINE (ME60)
31 Effect of medical ozone therapy on renal Controlled clinical trial Chronic hepatitis 43/85 35 µg/mL Clinical Renal function parameters improved n.a. 1.0
blood flow and renal function of patients with Middle- 9 MAH/pat improve- P < 0.01 No adverse event Safe IIa
chronic severe hepatitis. aged In total: 430 ment
Chinese medical journal VOL:123(18); p.2510-
3/201009/
ND = ME21034619 MEDLINE (ME60)
37 Preliminary results of ozone therapy as a Controlled clinical trial Chronic hepatitis C 40/52 25–60 µg/ml Clinical Statistically significant improvement in 1.0
possible treatment for patients with chronic In total 1740 improve- liver-specific parameters P ≤ 0.05 IIa
hepatitis C. ment
Journal of alternative and complementary
medicine (New York, N.Y.) VOL:17(3); p.259-
63/201103/
ND = ME21417811 MEDLINE (ME60)
38 Effects of major ozonated autohemotherapy Randomized Age-related 70/140 20 µg/mL Visus ROS reactive oxygen species No adverse event 1.1
in the treatment of dry age related macular controlled clinical trial, macular Elderly improve- P < 0.05 Safe Ib
degeneration: a randomized controlled degeneration ment
clinical study. (dry form) P < 0.05
International journal of ophthalmology VOL:5
(6); p.708-13/2012/
ND = ME23275905 MEDLINE (ME60)
39 Combination of LC-MS- and GC-MS-based Safety n.a. n.a. Release of plasticizers Suspected adverse
metabolomics to study the effect of ozonated Chemical analysis of effect using plastic bags
autohemotherapy on human blood. blood bags in MAH
Journal of proteome research VOL:11(12);
p.6231-41/20121207/
ND = ME23148940 MEDLINE (ME60)
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

Table 14. A/MAH 1.4. Result and assessment of literature search in MAH treatment (Medline).
Number of Results Statistics Quality
patients O3 conc. in µg/mL ranking
N1 /N* number of MAH Therapeutically Adverse events level of
Nr. Source Type Indication age treatments Clinical data relevant parameters /Safety statement evidence
40 Major ozonated autohemotherapy promotes Controlled clinical Acute cerebral 43/86 47 µg/mL Sign. Clinical No adverse event 1.0
the recovery of upper limb motor function in study infarction 30-80 yrs 1 MAH/pat improvem. Safe IIa
patients with acute cerebral infarction. In total: 43
Neural regeneration research VOL:8(5); p.461-
8/20130215/
ND = ME25206688 MEDLINE (ME60)
41 Time and time-frequency analysis of near- Controlled clinical case Acute stage in 4/9 40 µg/mL Clinical improvem. Reduction of ox stress n.a No adverse event 0.7
infrared signals for the assessment of ozone study MS middle aged 9 MAH/pat parameters Safe IIIa
autohemotherapy long-term effects in In total: 430
multiple sclerosis.
Conference Proceedings: . . . Annual
International
ND = ME24111149 MEDLINE (ME60)
42 NRF2 activation is involved in ozonated Safety n.a. n.a. 20/40/80 µg/ml Nrf2 activation No toxicity n.a.
human serum upregulation of HO-1 in pharmacology
endothelial cells.
Toxicology and Applied Pharmacology 267
(1):30–40/20130215/
ND = ME23253326 MEDLINE (ME60
43 Long-term improvement in refractory Clinical case reports Refractory 5/5 3-60 µg/mL Clinical, significant No adverse event 0.6
headache following ozone therapy. headache 44 ± 11 yrs 10 MAH/pat improvem. (VAS) Safe IIIb
Journal of Alternative and Complementary in total: 50
medicine (New York, NY) 19 (5):453–8/
201305/
ND = ME23215625 MEDLINE (ME60)
44 The evaluation of ozone and betahistine in Randomized, Tinnitus 27/68 10 MAH/pat Partly clinical No adverse event 1.0
the treatment of tinnitus. controlled clinical trial in total: 270 improvem. Safe Ib
European Archives of Oto-rhino-laryngology
ND = ME23100082 MEDLINE (ME60)
45 [Dynamics of local expression of connexin-43 Clinical study Skin infection, 60/60 MAH in total: Clinical improvem. Growth factor No adverse event 0.6
and basic fibroblast growth factor receptors in No control Diabetes 2 around 360 improvement Safe IIb
patients with skin and soft-tissue infections
against the background of diabetes mellitus
type II].
Vestnik khirurgii imeni I. I. Grekova 173 (4):47–
52/2014/
ND = ME25552106 MEDLINE (ME60)
OZONE: SCIENCE & ENGINEERING
17
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

18

Table 15. A/MAH 1.5. Result and assessment of literature search in MAH treatment (Medline).
No. of O3 conc. in Results Statistics Quality
patients µg/mL Therapeutically ranking
R. VIEBAHN-HÄNSLER ET AL.

N1 /N* No. of MAH relevant Adverse events Level of

Nr. Source Type Indication Age treatments Clinical data parameters /Safety statement evidence
46 Ozone autohemotherapy induces long-term cerebral Controlled clinical MS in acute 32/55 40 µg/mL Clinical improve-ment No adverse event 0.8
metabolic changes in multiple sclerosis patients. study stage In total: 32 Safe IIa
International Journal of Immunopathology and
Pharmacology 27(3):379–89/2014 Jul-Sep/
ND = ME25280029 MEDLINE (ME60)
47 Efficacy and safety of ozonated autohemotherapy in Controlled clinical Gout, arthritis 10/10 40 µg/mL Clinical improve-ment Improvement No adverse event 1.0
patients with hyperuricemia and gout: A phase I pilot case study 9 MAH/pat. VAS P = 0.027 of creatinine Safe IIIa
study. In total: 430 clearance
Experimental and Therapeutic Medicine 8 (5): 1423–27/
201411/
ND = ME25289033 MEDLINE (ME60
48 [Prolonged epidural analgesia and ozonated Limb ischemia Assessment not possible, no
autohemotherapy in complex surgical treatment at abstract, Russian language
patients with thromboangiitis obliterans and critical limb
ischemia].
Khirurgiia 82-8/2014/
ND = ME25272682 MEDLINE (ME60)
49 Is ozone pre-conditioning effect linked to Nrf2/EpRE Clinical case reports Healthy 6/58 yrs 35 µg/mL Nrf2 modulation No adverse event 0.6
activation pathway in vivo? A preliminary result. Pharmacology subjects 3 MAH/pat. Safe n.a.
in total:18
European Journal of Pharmacology 742:158–62/20141105/
ND = ME25218903 MEDLINE (ME60)
50 Does ozone autohemotherapy have positive effect on Case report Spinal epidural 1 case No literature available 0.4
neurologic recovery in spontaneous spinal epidural hematoma n.a.
hematoma?
The American Journal of Emergency Medicine 32 (8):949.
e1-2/201408/
ND = ME24602896 MEDLINE (ME60)
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

Table 16. B/MAH 1.1. Result and assessment of literature search in MAH treatment (Taylor & Francis).
No. of Results Statistics Quality
patients ranking
N1 /N* O3 conc. in µg/mL Therapeutically relevant Adverse events level of
Nr. Source Type Indication Age No. of MAH treatments Clinical data parameters /Safety statement evidence
B5 Mawsouf, M. N., T. T. Tanbouli Clinical Chronic hepatitis C 110/110 25–60 µg/mL Clinical improve-ment Improvement of liver specific No adverse event 0.8
and R. Viebahn-Hänsler. 2012. study, 23– In total: > 3120 MAH enzymes. Reduction of viral load Safe IIb
“Ozone Therapy in Patients no 58 yrs
with Viral Hepatitis C. Ten control
Years’ Experience.” Ozone: Sci.
Eng. 34: 451–458.
B4 Fathi, A., M. N. Mawsouf and Clinical Diabetic foot, chronic 63/63 MAH application could not be figured Clinical improve-ment No adverse event 0.8
R. Viebahn-Hänsler. 2012. study, nonhealing wounds out, see rectal insufflation Safe IIb
“Ozone Therapy in Diabetic no
Foot and Chronic, Nonhealing control
Wounds.” Ozone: Sci Eng 34:
438–450.
*N1 / N : number of ozone MAH treated patients (N1) in relation to the total number. N - N1 = number of patients as control.
OZONE: SCIENCE & ENGINEERING
19
 20 R. VIEBAHN-HÄNSLER ET AL.

Table 17. A/RI 1.0. Literature search RI Medline (2015-05-22; 03:01 p.m.).
DIMDI -Medline Direct 22.05.15 15:01
1. Ozone protective effects against PTZ-induced generalized seizures are mediated by reestablishment of cellular redox balance and A1
adenosine receptors.
ND = ME25258110 MEDLINE (ME60)
2. Ozone-oxidative preconditioning prevents doxorubicin-induced cardiotoxicity in Sprague–Dawley rats.
ND = ME25097769 MEDLINE (ME60)
3. Ozone oxidative preconditioning prevents atherosclerosis development in New Zealand White rabbits.
ND = ME23222311 MEDLINE (ME60)
4. Modulation of age-related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy.
ND = ME23172693 MEDLINE (ME60)
5. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy.
ND = ME23102757 MEDLINE (ME60)
6. Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.
ND = ME23046293 MEDLINE (ME60)
7. Cardioprotective effects of ozone oxidative preconditioning in an in vivo model of ischemia/reperfusion injury in rats.
ND = ME22862559 MEDLINE (ME60)
8. Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease.
ND = ME22796450 MEDLINE (ME60)
9. Reliable and effective oxygen-ozone therapy at a crossroads with ozonated saline infusion and ozone rectal insufflation.
ND = ME22420654 MEDLINE (ME60)
10. Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C.
ND = ME21417811 MEDLINE (ME60)
11. The effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits.
ND = ME20675916 MEDLINE (ME60)
12. Effect of ozone/oxygen mixture on systemic oxidative stress and organic damage.
Downloaded by [Hacettepe University] at 13:51 27 June 2016

ND = ME20017603 MEDLINE (ME60)

13. [The treatment of an acute paraproctitis].
ND = ME19405402 MEDLINE (ME60)
14. Therapeutic efficacy of ozone in patients with diabetic foot.
ND = ME16198334 MEDLINE (ME60)
15. Ozone therapy on rats submitted to subtotal nephrectomy: role of antioxidant system.
ND = ME16192672 MEDLINE (ME60)
16. Ozone therapy effects on biomarkers and lung function in asthma.
ND = ME16099337 MEDLINE (ME60)
17. Effektivnost’ razlichnykh metodik ozonoterapii pri sosudistykh oslozhneniiakh sakharnogo diabeta. [Efficacy of different methods of ozone therapy in
vascular complications of diabetes mellitus].
ND = ME12532590 MEDLINE (ME60)
18. Oxidative preconditioning affords protection against carbon tetrachloride-induced glycogen depletion and oxidative stress in rats.
ND = ME11481663 MEDLINE (ME60)
19. Labor de la enfermera en la aplicación de la ozonoterapia en retinosis pigmentaria. Enero-mayo, 1996. [The nurse’s work in the application of ozone
therapy in retinitis pigmentosa. January–May 1996].
ND = ME09934231 MEDLINE (ME60)
20. Ozone oxidative preconditioning: a protection against cellular damage by free radicals.
ND = ME09792340 MEDLINE (ME60)
21. Does ozone alleviate AIDS diarrhea?
ND = ME08409316 MEDLINE (ME60)
22. Ozon-kislorodnaia terapiia v proktologii. -[Ozone-oxygen therapy in proctology].
ND = ME02336632 MEDLINE (ME60)
23. The role of ozone/oxygen in clindamycin-associated enterocolitis in the Djungarian hamster (Phodopus sungorus sungorus).
ND = ME03951192 MEDLINE (ME60)
 OZONE: SCIENCE & ENGINEERING 21

Table 18. B/RI 1.0. Literature search in Taylor & Francis: Ozone: Science & Engineering (2015-06-03; 12:55 p.m.).
Viebahn-Hänsler, R., O.S. León Fernández and Z. Fahmy 2012. „Ozone in medicine: The low-dose ozone concept.
1 Guidelines and treatment strategies“. Ozone: Sci. Eng. 34: 408-424.
2 Mawsouf M. N., T. T. Tanbouli, R. Viebahn-Hänsler. 2012. „Ozone Therapy in Patients with viral hepatitis C – ten years experience“. Ozone: Sci. Eng. 34:
425-431.
3 Díaz Gómez, M. 2004. “Effect of -tocopherol during in vitro ozonation of methyl linoleate: its imolication in ozone therapy”. Ozone: Sci. Eng. 26: 189-
194.
4 Díaz-Soto, M. T., A. F. Pérez, J. D. Vaillant, A. Mallok . R. Viebahn-Hänsler, S. Menéndez Cepero, O. S. León Fernández 2012. “Ozone therapy ameliorates
nervous system disorders and plasmatic oxidative stress in patients during Ethanol Withdrawal-A pilot study”. Ozone: Sci. Eng. 34: 432-437.
5 Calunga, J.L., S. Menendez, R. Léon, R.Chang, S.Guanche, D.Balbín, A. Zayas, J. Gará. 2012. „Application of ozone therapy in patients with knee
osteoarthrosis“. Ozone: Sci. Eng. 34, 469-475.
6 Rilling, S. „The basic clinical application of ozone therapy“. 1985. Ozone: Sci. Eng. 7: 259-274.
7 Fathi, A. M., M. N. Mawsouf, R. Viebahn-Hänsler. . 2012. „Ozone Therapy in Diabetic Foot and Chronic, Nonhealing Wounds“.Ozone: Sci. Eng. 34: 438-
450.
8 Bocci, V., C. Borelli, G. Corradeschi, A. Diadori, G. Fanetti, G. Valacchi. 2001. „Ozone in Medicine“. Ozone: Sci. Eng. 23: 207-217.
9 Díaz-Soto, M.T., A. Fraga Pérez, J. Dranguet Vaillant, A. Mallok, R. Viebahn-Hänsler, S. Menéndez Cepero,
O. S. León Fernández. 2012. “Ozone Oxidative Postconditioning protects against the injury associated to Alcohol Withdrawal Syndrome in rats”. Ozone:
Sci. Eng. 34: 425-431.
10 Copello, M., S. Menéndez, F. Hernández.. 2012.
“Ozone therapy in Retinitis Pigmentosa patients. Clinical Evolution and oxidative stress behaviour in Retinitis Pigmentosa patients treated with ozone
therapy during 20 years”. 2012. Ozone: Sci. Eng. 34: 475-483.
Downloaded by [Hacettepe University] at 13:51 27 June 2016
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

22

Table 19. A/RI 1.1. Result and assessment of literature search in Rectal Insufflation (Medline).
R. VIEBAHN-HÄNSLER ET AL.

No. of O3 conc. in Results Quality

patients µg/mL Statistics ranking
N1 /N* No. of RI Therapeutically relevant Adverse events /Safety level of
Nr. Source Type Indication Age treatments Clinical Data parameters statement evidence
5 Long-term control of refractory hemorrhagic radiation Clinical study, Radiation 17/17 5; 20; 30 µg/ Stat.sign. clinical Hb; HRP No adverse event 0.8
proctitis with ozone therapy. no control proctitis 42-80 yrs mL improvement p < 0.001 Safe III
ND = ME23102757 MEDLINE (ME60) ≥ 340 RI
6 Ozone therapy as add-on treatment in fibromyalgia Clinical study, Fibromyalgia 36/36 40 µg/mL; Stat.sign. clinical Total scores (FIQ) No adverse event 0.9
management by rectal insufflation: an open-label pilot no control 864 treat- improve-ment decreased significantly Minor irritations: IIb
study. ments flatulence
Journal of Alternative and Complementary Medicine 19
(3):238–42/201303/
ND = ME23046293 MEDLINE (ME60)
8 Effects of ozone therapy on haemostatic and oxidative Random. Coronary artery 26/103 50 µg/mL Stat. sign. Prothrombin sign. No adverse event 1.1
stress index in coronary artery disease. controlled disease ≥ 80 yrs 520 treat- improved Safe Ib
ND = ME22796450 MEDLINE (ME60) clinical study ments p < 0.001
10 Preliminary results of ozone therapy as a possible Controlled clin. Hepatitis C 40/52 40 µg/mL Sign. clinical Liver specific enzymes No adverse event 1.0
treatment for patients with chronic hepatitis C. Journal of study All ages 1610 treat- improve-ment improved sign. Safe IIa
Alternative and Complementary Medicine 17 (3):259–63/ ments
201103/
[ND = ME21417811 MEDLINE (ME60)
14 Therapeutic efficacy of ozone in patients with diabetic Random. Diabetic foot 52/101 50 µg/mL Stat sign Clinical Diabetes related param. No adverse event 1.1
foot. controlled Diab. 2 20 60 yrs 1040 treat- improve-ment improved Safe Ib
European Journal of Pharmacology 523 (1–3):151–61/ clinical ments p ≤ 0.01
20051031/ study
[ND = ME16198334 MEDLINE (ME60)
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

Table 20. A/RI 1.2. Result and assessment of literature search in Rectal Insufflation (Medline).
No. of O3 conc. in µg/ Results Statistics
patients mL
N1 /N* No. of MAH Therapeutically relevant Adverse events Quality ranking level
Nr. Source Type Indication age treatments Clinical data parameters /Safety statement of evidence
16 Ozone therapy effects on biomarkers and Controlled Asthma 27/113 50 µg/mL Stat. sign. clinical Stat. sign. improvement of No adverse event 1.0
lung function in asthma clinical trial, 15-50 yrs 1620 improvement IGE HDLA-DR Safe IIa
Archiv of Medical Research 36 (5):549–54/ treatments
2005,
ND = ME16099337
17 Effektivnost’ razlichnykh metodik ozonoterapii Clinical trial Diabetes 118 Clinical improve- In Russian language: could n.a.
pri sosudistykh oslozhneniiakh sakharnogo ment not be evaluated
diabeta.—[Efficacy of different methods of
ozone therapy in vascular complications of
diabetes mellitus].
ND = ME12532590 MEDLINE (ME60)
19 Labor de la enfermera en la aplicación de la Nurse study Retinitis Could not be evaluated n.a.
ozonoterapia en retinosis pigmentaria. Enero- pigmentosa
mayo, 1996.—[The nurse’s work in the
application of ozone therapy in retinitis
pigmentosa. January-May 1996].
Revista Cubana de Enfermería 14(2): 99–102/
1998
ND = ME09934231 MEDLINE (ME60)
21 Does ozone alleviate AIDS diarrhea? Journal of Case study Diarrhea in HIV 5/5 Clinical improve- No adverse event 0.6
Clinical Gastroenterology 17(2): 142–5/199309/ patients ment in 4 pat. Safe IIIb
ND = ME08409316 MEDLINE (ME60)
22 Ozon-kislorodnaia terapiia v proktologii.— Preclinical n.a. n.a. n.a. n.a. n.a.
[Ozone-oxygen therapy in proctology]. study
Terapevticheskii Arkhiv 62(2): 93–8/1990/
[ND = ME02336632 MEDLINE (ME60)
25 Knoch, H.G. & W. Klug. Controlled Colitis 248 30 µg/mL Clinical No adverse event 0.9
Rektale Ozon-Sauerstoff-Anwendung in der clinical study 3540 improvement Safe IIb
Proktologie.
In (Hrsg.)
Ozon-Handbuch, ecomed Landsberg, edited
by E.G. Beck, E.G. and R. Viebahn-Hänsler.
1995.
OZONE: SCIENCE & ENGINEERING
23
 Downloaded by [Hacettepe University] at 13:51 27 June 2016

24

Table 21. B/RI 1.1. Result of literature search in RI treatment (Taylor & Francis).
R. VIEBAHN-HÄNSLER ET AL.

No. of O3 conc. in µg/ Results

patients mL Statistics Adverse events Quality
N1 /N* No. of MAH Therapeutically relevant /Safety ranking level
Nr. Source Type Indication Age treatments Clinical data parameters statement of evidence
B2 Ozone Therapy in Patients with Viral Hepatitis Clinical study Chronic 110/110 25-60 µg/mL Clinical Improvement of liver specific No adverse 0.9
C. Ten Years´Experience hepatitis C 23-58 yrs > 3120 treat- improvement enzymes event IIb
Ozone: Science & Egineering 34:(2012) 451-458 ments Safe
B4 Ozone Therapy Ameliorates Nervous System Clinical study Alcoholics 10/10 20-35 µg/mL Clinical Stat. sign. improvement of antiox. No adverse 0.9
Disorders and Plasmatic Oxidative Stress in av. 34 yrs 200 treat-ments improvement and ox. stress event IIb
Patients During Ethanol Withdrawal—A Pilot Safe
Study”
Ozone: Science & Engineering 34: 432-437
(2012)
B5 Application of Ozone Therapy in Patients Controlled clinical Osteo- 42/52 25-40 µg/mL Clinical Stat. sign. improvement of antiox. No adverse 1.0
with Knee Osteoarthritis trial arthritis 45-65 yrs 1500 treat-ments improvement and ox. stress event IIa
Ozone: Science & Engineering 34:469–475 P < 0.05 Safe
(2012)
B7 Ozone Therapy in Diabetic Foot and Chronic, Clinical trial Diabetes 2 63/63 30-40 µg/mL Sign. clinical No adverse 0.8
Nonhealing Wounds. Ozone: Science & elderly ≥ 630 treat- improvement event IIb
Engineering 34:438-450 (2012) ments Safe
B10 Copello, M., S. Menéndez, and F. Hernández. Controlled clinical Retinitis 40/56 40 µg/mL Sign. clinical Visual improvement No adverse 1.0
2012. study pigmentosa All ages 32.000 treat- improvement P < 0.05 event IIa
“Ozone Therapy in Retinitis Pigmentosa ments Safe
Patients
Clinical Evolution and Oxidative Stress
Behavior in Retinitis Pigmentosa Patients
Treated with Ozone Therapy During 20 Years.”
Ozone: Science & Engineering 34:475–483.