Ozone (O3) is an allotropic form of oxygen, primarily known for its ecological properties, industrial application and therapeutic effects 1.
Ozone therapy is still a controversial form of alternative therapy. Questions persist in terms of its potential toxicity as an oxidant agent versus its reported clinical efficacy. Many systematic reviews on ozone therapy in general or in specific conditions have been published, especially in the Centre for Reviews and Dissemination (http://www.york.ac.uk/inst/crd/). Search of the Centre for Reviews and Dissemination (http://www.crd.york.ac.uk/) using ‘ozone therapy’ as the search term on June 2012 retrieved 13 results, including systematic reviews and health technology assessments. A PubMed search on the same date retrieved 2226 hits using the following search strategy (‘ozone’ [MeSH Terms] OR ‘ozone’ [All Fields]) AND (‘therapy’ [Subheading] OR ‘therapy’ [All Fields] OR ‘therapeutics’ [MeSH Terms] OR ‘therapeutics’ [All Fields]).
Published studies on the use of ozone in dentistry 2,3, rheumatic diseases 4 and low back pain 5 did not provide sufficient evidence for the use of ozone in such conditions.
A Health Technology Assessment report on ozone therapy reached the same conclusion, 6, which was adopted by the Malaysian Ministry of Health 7. The report stated that ‘current data on the usage of ozone therapy as a therapeutic option for various health conditions lacks sufficient safety and therapeutic advantage over available conventional therapeutic modalities’.
In this review, a source that is typically not published in the known medical databases and may be considered as grey literature was evaluated. Review of postgraduate theses on ozone represents a challenge, but it may provide new evidence on the safety and effectiveness of ozone therapy, taking into consideration the limitations linked to postgraduate studies. The conclusion of this review may complement conclusions from other reviews and may serve as a guide to extend these reviews to other grey literature sources, including postgraduate studies in other countries. Egypt was selected as a feasible model and is recognized as one of the internationally represented schools in ozone therapy, which was practiced in Egypt until it was banned in 2009. Egypt may be the only country in the region with this many number of postgraduate studies on ozone therapy.
The objective of this review was to assess the clinical safety and effectiveness of ozone therapy in specific medical conditions, published in postgraduate theses in Egypt. The retrieved theses were grouped according to PICOS elements (population – intervention – comparator – outcome – study design) for each specific disease addressed 8.
Search and inclusion criteria
The database of the Egyptian Universities’ Library Consortium and databases at each university were searched. Direct visits were also made to all universities in search of input from experts in the field and to retrieve the full-text theses. The studies included were postgraduate theses in Egypt that evaluated ozone therapy as an intervention for any disease or condition in any age group and compared ozone therapy with any or no other intervention. In addition, studies were not excluded on the basis of area of study, language restriction or date, but they must have been published before September 2010.
The theses included in this study were selected in three stages. During the first stage, all theses related to ozone were retrieved. During the second stage, all of the theses retrieved were manually filtered to include only theses on ozone therapy in any disease or condition. In the third phase, only clinical trials and systematic reviews were included to generate evidence. However, the reviews identified were not systematic reviews and they were therefore excluded.
The following data were extracted and collected in an Excel spread sheet: thesis title, author, university, college, degree, disease or condition addressed, and PICOS. Two reviewers were involved separately for each thesis. The authors of the theses were not contacted for further details. For each specific condition, the groups of theses addressing the same condition were reviewed. Review teams were allocated to each condition to conduct study appraisal.
Method of study appraisal
To critically appraise review theses, the following questions were addressed: was the review question clearly defined in terms of population, interventions, comparators, outcomes and study designs (PICOS)? Was the search strategy adequate and appropriate? Were there any restrictions on language, publication status or publication date? Were preventative steps taken to minimize bias and errors in the study selection process? Were the appropriate criteria used to assess the quality of the primary studies and were preventative steps taken to minimize bias and errors in the quality assessment process? Were preventative steps taken to minimize bias and errors in the data extraction process? Were adequate details presented for each of the primary studies? Were appropriate methods used for data synthesis? Were differences between studies assessed? Were the studies pooled, and if so, was it appropriate and meaningful to do so? Finally, do the authors’ conclusions accurately reflect the evidence that was reviewed?
For randomized-controlled trials, the following criteria were applied: the appropriateness of the study design to the research objective; the risk of bias (random allocation, concealment, group similarity, blindness, dropout imbalance); the choice of outcome measure; statistical issues; the quality of reporting; the quality of intervention; and generalizability. Two independent reviewers were responsible for the evaluation process.
A total of 63 theses were evaluated manually. The manual evaluation excluded duplicates (two theses) and basic science (not related to medicine) theses (four theses), bringing the total to 57 included studies. The majority of the studies were from Cairo University (25 theses), followed by Al-Azhar University (11 theses). Twenty-nine of the 57 theses were from departments of medicine, followed by departments of dentistry (13 theses) and physical therapy (nine theses). Out of the 57 studies included, Master’s theses accounted for 45 studies and the remaining were MD or equivalent. Thirty of the studies were published in 2008–2009.
A total of nine reviews were not systematic, but were narrative, and therefore failed to attain the minimal requirement for inclusion. The final number of studies included was 28 after excluding animal and in-vitro studies in addition to reviews (Fig. 1).
Safety of ozone therapy
No theses evaluated the safety of ozone or reported cases of side effects or severe adverse events.
- Dental infection and recovery (Table 1): All of the studies suggested a favourable effect of ozone in dental infections, in facilitating faster recovery after extraction or implantation and improving pain and mobility in cases of temporomandibular joint derangement. However, there was insufficient evidence to support its use because of the small number of studies included and their poor quality 9–18.
- Musculoskeletal disorders (Table 2): Four studies with fair to good quality suggested that an intra-articular or a local injection of ozone may have a favourable effect in cases of frozen shoulder (one study) 19, low back pain (one study) 20, temporomandibular joint disorders 14 and vertebral spondylosis (one study) 23. The small number of studies included in this review cannot provide sufficient evidence for the use of ozone in the treatment of musculoskeletal disorders. Rectal insufflation combined with minor autohaemotherapy in one study had a favourable effect when used to treat rheumatoid osteoarthritis 22. Two studies evaluating ozone saunas concluded that they may relieve cervical muscle spasms and muscle fatigue 21,25. One study, on using ozone therapy in chronic arm lymphoedema following radiotherapy, also showed a favourable effect of ozone 24.
- Diabetes mellitus (Table 3): Three studies 26–28 using major or minor autohaemotherapy and rectal insufflations showed favourable effects on insulin-resistant parameters (one study), oxidative protein products (one study) and peripheral neuropathy (one study). Unfortunately, the evidence is not sufficient because of the small number of studies and their low quality. One study suggested a positive effect of rectal insufflation and the placement of an ozone-filled bag on a diabetic foot 29.
- Chronic diseases (Table 4): One study presented insufficient evidence for the rectal use of ozone to treat asthma 30. Another study evaluated autohaemotherapy in the treatment of tinnitus 31. The effect of rectal ozone with a locally applied ozone-filled bag may have a favourable effect in cases of diabetic ulcers and chronic ulceration because of obliterative atherosclerosis 32. However, ozone therapy was less effective than acupuncture in obesity 33.
- Obstetrics and gynaecology (Table 5): One study suggested that the use of rectal ozone is effective in the treatment of toxoplasmosis, but the quality of the study was poor 34. In another study, the use of rectal ozone in addition to methyldopa was superior to methyldopa alone in hypertensive pregnant women, and the quality of the study was fair 35.
This review identified a relatively large number of relevant theses on the use of ozone therapy in different illnesses, which may reflect an increasing interest in this modality of therapy. In this review, we applied high standard quality criteria to critically appraise the theses included, which may explain why they failed to attain a high-quality level.
All the theses were focused on effectiveness without commenting on safety issues, which should be considered even if the primary objective is effectiveness.
The favourable effects of ozone therapy in dentistry reported in the retrieved theses in our study 9–18 were in agreement with other published studies 2,3. The small number of theses included and their low quality may be the reason. In musculoskeletal disorder, the only growing evidence on the use of ozone was in low back pain 5, which was in agreement with the thesis included on the use of ozone in low back pain 20. Other theses on the use of ozone in diabetes mellitus, chronic illnesses and obstetrics and gynaecology, although reporting favourable results of ozone therapy in different illnesses, lacked the high quality required to generate scientific evidence. The small number of studies in each indication is another major obstacle for generating evidence.
An important limitation of this study is that postgraduate theses were not designed from the beginning with quality standards to generate evidence. They were mainly exploratory studies that need further quality improvements. Also, review of all ozone therapy indications in one review may be a general technical assessment that needs further detailed review, at least for promising indications.
This review of postgraduate theses in Egypt on the use of ozone therapy does not support any therapeutic advantages over the current conventional treatments for a variety of diseases, taking into consideration the small number of studies and their limited quality. Nonetheless, postgraduate theses may serve the medical community as an additional source of information. The information presented in postgraduate theses may lead to further research or may raise important research questions to be addressed in more standard scientific ways.
More well-designed and well-conducted double-blind randomized clinical trials with adequate sample size, and carefully standardized methods of measurement and analyses are required to evaluate the possible use of ozone as a treatment modality in various illnesses.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2013 Egyptian Public Health Association
alternative; complementary medicine; Egypt; ozone; post graduate