REPORT ON CLINICAL TRIALS BY

MICHAEL T. CARPENDALE M.D.  AND  JOHN GRIFFIS M.D

 

ABSTRACT

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

INTRODUCTION

Ten years after the isolation, description and identification of HIV, a safe and effective treatment is yet to be found.

During this period studies have been made on the use of Medical Ozone in the in vitro inactivation of HIV, and pilot studies on its use in treating patients with asymptomatic HIV infection and also patients with terminal AIDS.

The results of these studies and others provide compelling reasons why medical ozone should be evaluated (in North America) as a potential treatment for HIV and its infections in man.

This paper is a brief review of the most important reasons for this line of thinking. These fall in to six major areas:

1. The use of ozone in the treatment of infectious diseases.

2. Ozone as a virucidal agent.

3. Ozone as a broad spectrum bactericidal, protozaicidal and fungicidal agent.

4. Ozone as a stimulator of the immune system. 

5. Ozone ancillary factors.

6. Ozone in clinical studies.

a. Ozone in the treatment of early asymptomaticHIV infection.

b. Ozone in the treatment of terminal HIV infection - AIDS.

THE USE OF OZONE IN THE TREATMENT OF INFECTIOUS DISEASES.

Ozone is the triatomic allotrope of oxygen with a high electrovoltaic potential. Medical Ozone (hereafter called ozone) is a gaseous mixture of ozone and pure oxygen where ozone constitutes from 0.1 to 5.0% (1.0 to 100ugO3/mlO2) and oxygen forms the larger proportion (99.9 to 95%) of the mixture. It is not to be confused with ozone generated from air which contaminates the mixture with oxides of nitrogen. It is produced by a medical ozone generator by flowing pure oxygen through a high voltage field. The concentration of ozone in the mixture is dependent on the voltage, gas flow rate and the space between the electrodes. Well designed generators will consistently deliver very accurate ozone concentrations down to 1-0 ugO3/mlO2.

The first practical use of ozone in medicine was reported in 1891 when laboratory tests proved it to be an effective bactericidal agent in the disinfection of polluted drinking water (1).

One hundred years later it is now recognized as the most effective germicidal agent for this purpose because of its broad spectrum effect including not only bacteria, but viruses and protozoa as well. Also, (because of) the fact that it leaves no residue, except for oxygen, and has no adverse effects or toxicity on man (2). The sterilization of drinking water is still the main use of ozone in medicine.

Although its germicidal properties were recognized as possibly useful in the treatment of infectious disease, technical problems, e.g., generation, accurate dosage, monitoring, dispensing and application of a strong and potentially toxic gaseous oxidant prevented any significant practical use in treatment. But between 1930 and 1940 three pioneers developed new apparatus and techniques overcoming many of the technical problems, making it possible to use ozone in the treatment of infectious disease: Fisch in dentistry (3), Payr in surgery (4) and Aubourg in medicine (5).. Their work provided a firm foundation for the scientific use of Ozone in the Treatment of Infectious Disease in Man.

Initially treatment was mainly for local superficial infections such as, ulcers, abscesses and fistulae, etc., where ozone concentration ranged from 2.0ugO3/mlO2, as a stimulant for healing for a local superficially infected abrasion, to 100.0ugO3/mlO2 as a potent debriding agent for a deep seated necrotic decubitus ulcer. But Payr showed that with care and time ozone gas could be injected directly subcutaneously, intramuscularly or with more time intravenously or intraarterially without adverse effect (4). Later Aubourg showed that insufflating ozone into the colon was a simple, safe and effective way for getting a large dose into the body for a widespread systemic effect (5).

Today the main ways of administering ozone for a systemic effect are by rectal colonic insufflation or by autohemotherapy, where venous blood is withdrawn into a vacutainer flask, injected with ozone and then reinfused into the blood stream. Autohemotherapy has to be performed in a physician's office, but rectal insufflation can be done at home by an intelligent, responsible and appropriately trained adult. Dosages by these methods are concentration 10.050.0ugO3/mlO2 for total doses of 20-40mg ozone.

In 1944 Pribluda, comparing the efficiency of ozone and the new antibiotic drug penicillin, reported the advantages of ozone. It worked well with many organisms unaffected by penicillin, produced marked effect in detoxification of septicemia, and marked analgesic effect on many patients with pain, especially rheumatoid arthritis.

With the advent of wide spectrum antibiotics, and the convenience of oral tablets, ozone became displaced in most practices in the treatment of infectious disease.

OZONE AS A VIRACIDAL AGENT

Ozone effectively inactivates enveloped and non-enveloped viruses when introduced into suspensions in water effluent and cell culture media.  In man ozone was first reported effective in 1983 in the treatment of Herpes Simplex and Zoster virus, and Hepatitis B virus.  The first report of the inactivation of HIV by ozone was in 1988 at the IV International Conference of AIDS at Stockholm, Sweden. 

In summarizing their results the authors write:

"Results of experiments to date indicate that ozone has the ability to inactivate extracellular HIV in body fluids and inhibit growth of intracellular HIV at concentrations that are benign to cells.

These findings support the contention that the beneficial results reported on ARC/AIDS patients treated with ozone may be due to its virucidal activity as has also been hypothesized in the successful treatment of patients with Hepatitis B virus. 

The in vitro inactivation of HIV Type 1 by ozone has also been demonstrated by using a device designed to deliver a constant source of given concentration of ozone to fluids containing HIV- 1. (Here again ozone was found to inactivate HIV in a dose dependent manner. Greater than 11 log inactivation was achieved within two hours at a concentration of 1,200 p.p.m. ozone similar concentrations of ozone had minimal effect on factor VIII activity in both plasma and immune affinity-purified preparations of factor VIII treated for the same period. The authors conclude that the antiviral effects of ozone include viral particle disruption, reverse transcriptase inactivation, and/or a perturbation of the ability of the virus to bind to its receptor on target cells. They indicate that ozone treatment offers promise as a means to inactivate human retroviruses in human body fluids and blood product preparations.

 OZONE AS A BROAD SPECTRUM BACTERICIDAL, PROTOZOICIDAL AND FUNGICIDAI, AGENT

The literature on the ozonation of microorganisms is voluminous, and most of it related to disinfection of water. Langlais et al pp. 224-229 have a very well referenced small section "Ozone Inactivation Mechanism and Comparison of C.T. Values for Selected Organisms" which describes effects of ozone on different bacteria, viruses, spores, amoebae, and the special case of free amoebae, Giardia and Cryptosporidium.

The importance of this in the treatment of HIV is clearly because of all the associated infections, particularly opportunistic ones. Many of these are resistant to antibiotics but nearly all of them are inactivated by ozone at levels that are not toxic to man. In the treatment of AIDS patients with ozone alone, one will see common secondary infections such as herpes simplex, folliculitis or tinea pedis and sycosis barbae clearing up in a few days after starting therapy.

OZONE AS A STIMULATOR OF THE IMMUNE SYSTEM

HIV was originally named the immunodeficiency virus because in infected patients of the very obvious systems, signs and laboratory findings indicating a massive attack and subsequent collapse of the immune system. This was brought about by a virus that was primarily attacking the T4 lymphocyte and many other cells in the immune system. Clearly the treatment required use of a virucidal agent that inactivated HIV, and if possible at the same time stimulated the immune system. Although ozone was always primarily thought of as a potent germicide and disinfectant, it was also recognized as a potent immunostimulant.  Recently in some classical laboratory studies Bocci and colleagues have confirmed the fact that ozone acts on monocytes and lymphocytes as an inducer cytokine in the production of interferon (IFN) and tumor necrosis factor, and probably many more immune functions as well.  Bocci hypothesizes that these cytokines in turn can activate other lymphoid cells leading to immunostimulation without side effects.

Ozone in the Treatment of Terminal HIV Infection - AIDS.

A small pilot study has been completed on the effect of ozone in the treatment of intractable diarrhea of unknown etiology in patients with AIDS.  In this study five patients with AIDS and intractable diarrhea of unknown etiology, were treated with daily colonic insufflations of medical ozone for 21 to 28 days. The daily dose of ozone ranged from 2.7 to 30mg. Three of the four patients whose diarrhea was of unknown etiology experienced complete resolution, and one patient had marked improvement. The fifth patient, whose diarrhea was due to Cryptosporidium, experienced no change. No consistent change in the absolute number of helper (CD4) or suppressor (CD8) lymphocytes was detected, and no obvious changes were seen in the pO2 or the results of routine hematologic and blood chemistry studies. Patients had mild to moderate local discomfort during ozone administration early in the course of treatment, but no adverse systemic effects were observed. The results of the present series suggest that medical ozone administered by rectal insufflation is simple, safe and effective in the treatment of intractable diarrhea in patients with AIDS.

CONCLUSION

The studies reviewed indicate the following:

1. Ozone has the ability to inactivate extracellular HIV in body fluids in a dose dependent manner and inhibit growth of intracellular HIV at concentrations that are benign to cells and usually stimulating to cells of the immune system.

2. Ozone is a low toxicity broad spectrum germicidal agent that has demonstrated a facility for successfully treating many of the organisms that produce secondary infections in the AIDS patient.

3. Ozone is a strong immunostimulant and when mixed with blood alone has the ability to produce many cytokines such as IFN and TNF. It seems likely that it will become recognized as an important (? ideal) cytokine inducer.

4. Ozone given for a systemic effect produces important ancillary factors such as increased oxygen utilization, tissue perfusion and membrane permeability all of which aid the body's resistance to infection.

5. Ozone in the treatment of early asymptomatic HIV+ve patients has a marked stimulatory effect on CD4 and CD8 cells, differentially increasing their numbers, and normalizing the ratio greater than 1.0. In addition, it has shown a marked decrease in the viral load in one (out of two) patients. Both patients remarked on their positive feelings of high energy and wellbeing while on ozone as opposed to when they had not been taking it for a few weeks. 

6. Ozone in the treatment of intractable diarrhea in AIDS patients resulted in complete resolution in 60%, marked improvement in 20% and no change in 20%. Resolution (elimination) of secondary infections were seen in herpes simplex, folliculitis or tinea pedis and sycosis barbae in a few days after.

Patients all felt less toxic, much less discomfort and much more energy. No adverse effects were reported.

In summary, these studies show that ozone treatment is safe. There is a wealth of anecdotal experience with its use to treat a variety of infectious diseases, and abundant evidence that it is virucidal, bactericidal, fungicidal and protozoicidal.

Although the optimum dose of ozone therapy needs to be determined for each infection, it is time to begin considering ozone (in North America) as we would any other promising anti-infective, and carefully assess its potential through well designed treatment protocols.

All reviewed studies just reconfirm the germicidal efficacy of ozone at non-cytotoxic concentrations and the immunostimulant effects at the same dosage. Simultaneously HIV patients and physicians the world over are looking for a drug which is both germicidal and immunostimulant. Surely we can get this drug, these patients and our act together for the benefit of all.

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Dr. Carpendale, M.D. is an internationally renown medical researcher of the highest degree of scientific integrity.  His clinical research studies at the San Francisco Veterans Hospital were carried out with the full knowledge and permission of the FDA.