Contacto para correspondencia: G. Martínez-Sánchez Medinat srl Clinic, Vía Fazioli 22, 60021 Camerano, Italy. Tel. +39 071 731076 Fax. +39 071 731347. E.mail: gregorcuba@yahoo.it

Sugerencia sobre cómo citar este artículo:

Gregorio Martínez-Sánchez, Silvia Menéndez-Cepero, Mirta Copello, Silvia Díaz-Llera, Lamberto Re (2012). Rectal insufflations are a valid way in ozonetherapy. Revista Española de Ozonoterapia. Vol. 2, nº 1, pp. xx-xx.

To the editor:

We read with great interest the manuscript entitled: “Oxygen-Ozone Therapy is at a Cross-Road” Rev. Esp. Ozono. 1(1):74-86.¹

First, we noted that some of the criteria considered by the authors do not appear to fit with reality. In the section: A few of the present methodologies are of doubtful value and may be dangerous or ineffective it is mentioned that the reason why Cubans do not use major autoemotherapy is because: “[…] every day they have to treat thousands of patients, it appears impossible to perform M-O3-AHT for lack of time and money”. Authors should know that the Cuban health system is well recognized by international authorities. For instance: according to the World Health Organization, Cuba provides a doctor for every 170 residents, and has the first highest doctor-to-patient ratio in the world. Even under the difficult economic situation, the reason to use or ban a medical procedure in Cuba is not based on time or money, but on clinical effectiveness and low rate of side effects. Cuba is the only nation which has a specialized center for ozone research. This center provides the preclinical and clinical evidence to support the medical application of this therapy.

Secondly, with regard to the rectal insufflations the manuscript says: “Firstly, the O3 concentration is too high and during prolonged use may be mutagenic; secondly, this route, being so uncertain, should not be used in controlled clinical trials”. Actually, the biological effect of O3 by rectal insufflations has been demonstrated extensively either experimentally^2-4 or clinically.^5-9 Furthermore, preclinical studies demonstrated its low toxicity.^3,10 Nowadays, the current maximal dose used in Cuba for this procedure is 200 mL O2/O3 with the O3 concentration of 40 μg/mL (O3 dose: 8 mg). Prospective clinical trials include the adjustment of the doses according to the redox diagnostic and imply the application of weekly progressive doses of 3.75, 6 and 7 mg for patients with redox index¹¹ 1 and 2 (normal or medium); 2.0, 3.25, 4.5 and 7 mg for patients with redox index 3 (high) and no therapy for patients with redox index 4 (critical). The therapeutic effectiveness of ozone by the rectal way is not uncertain. Rectal insufflation is the most harmless technique (practically free of adverse effects) and the most economic way of dosing ozone. Genotoxicity of therapeutic ozone was particularly studied in Cuba. Ozone autohemotherapy was proved to be neither clastogenic nor inducer of sister chromatic exchanges in cultured human lymphocytes. Certainly, ozone being a potent oxidant, primary DNA damage is evident after its rectal application in rats not only in colorectal cells, but also in peripheral leukocytes. However, after 72 h from the last exposure a significant decrease of DNA damage was observed in both cell types, indicating an evident recovery of the DNA primary damage induced by the treatment.¹⁰

The largest clinical trial using O3 rectal insufflations was done in Cuba, by Copello and Menendez¹² in patients with retinitis pigmentosa. They followed those patients who received O3 therapy every 6 months, for 25 years and found a sustained maintenance of the visual capabilities with no side effects.¹² For such a chronic disease, where ozone therapy cycles have to be repeated for many years, the less invasive way of ozone administration is the rectal application. The use of repetitive cycles of autohemotherapy would produce blood vessel injury. In addition, mutagenic effect of ozone does not depend on the administration way. Major autohemotherapy also induces DNA damage in peripheral lymphocytes but, as during rectal application, the DNA repairing mechanisms  can reverse this damage (Diaz-Llera et al. 2011 on submission).¹³

Thirdly, the comment referred to a clinical trial in diabetic foot patients: “it seems that in only twenty days that dosage could cure (?) the diabetic foot in a number of patients treated with rectal ozone and topical ozonated oil” and cited a clinical trial that appeared in Eur. J. Pharmacol., 2005.⁶ The article properly reports improvement in blood glucose level, reduction in area and perimeter of the lesion, decrease in oxidative biomarkers, reduction in hospital stay and reduction in costs compared to traditional therapy. In the abstract it is textually written: “[… ] the healing of the lesions improved, resulting in fewer amputations than in the control group”.

Since nobody in Cuba claims to be so prodigious as to cure a diabetic foot in only 20 days, the expression used appears not elegant to the scientific dignity of people working for many years, with only limited resources, yes, but certainly adhering to strict scientific standards. The work of colleagues all over the world must be respected and the recognized experience must be used to help and build and not to destroy.

References

1. Bocci V, Borrelli E, Zanardi I, Travagli V. Oxygen-ozone therapy is at a cross-road. Revista Española de Ozonoterapia. 2011;1(1):74-86.
2. Seda Artis A, Aydogan S, Gokhan Sahin M. The effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits. Clin Hemorheol Microcirc.45(2-4):329-36.
3. Guanche D, Zamora Z, Hernandez F, et al. Effect of ozone/oxygen mixture on systemic oxidative stress and organic damage. Toxicol Mech Methods. 2010 Jan;20(1):25-30.
4. Gonzalez R, Borrego A, Zamora Z, et al. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats. Mediators Inflamm. 2004 Dec;13(5-6):307-12.
5. Romero Valdes A, Blanco Gonzalez R, Menendez Cepero S, Gomez Moraleda M, Ley Pozo J. [Arteriosclerosis obliterans and ozone therapy. Its administration by different routes]. Angiologia. 1993 Sep-Oct;45(5):177-9.
6. Martinez-Sanchez G, Al-Dalain SM, Menendez S, et al. Therapeutic efficacy of ozone in patients with diabetic foot. Eur J Pharmacol. 2005 Oct 31;523(1-3):151-61.
7. Hernandez Rosales FA, Calunga Fernandez JL, Turrent Figueras J, Menendez Cepero S, Montenegro Perdomo A. Ozone therapy effects on biomarkers and lung function in asthma. Arch Med Res. 2005 Sep-Oct;36(5):549-54.
8. Zaky S, Kamel SE, Hassan MS, et al. Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C. J Altern Complement Med. 2011 Mar;17(3):259-63.
9. Zaky S, Fouad EA, Kotb HI. The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study). Br J Clin Pharmacol. 2011 Mar;71(3):411-5. doi: 10.1111/j.1365-2125.2010.03851.x.
10. Diaz-Llera S, González-Hernández Y, Mesa JEG, Martínez-Sánchez G, Re L. Induction of DNA primary damage in peripheral blood leukocytes and exfoliated colorectal epithelial cells in rats treated with O3/O2 mix. International Journal of Ozone Therapy. 2009;8:217-21.
11. Hernandez FA. To what extent does ozone therapy need a real biochemical control system? Assessment and importance of oxidative stress. Arch Med Res. 2007 Jul;38(5):571-8.
12. Copello M, Menéndez S. Retinitis Pigmentosa patients treated with ozone therapy during 20 years. Cuban experiences. Revista Española de Ozonoterapia. 2011;1(1):13-22.
13. Díaz-Llera S, González-Mesa JE, González-Hernández Y, Wong R. Study of O3-O2 therapy in patients by single cell gel electrophoresis assay  On submission. 2011.