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Rivista Italiana di Ossigeno-Ozonoterapia 1: 149-153, 2002 A Novel Therapeutic Option for Chronic
Fatigue Syndrome and Fibromyalgia
Department of Surgery and Biomedical Engineering and *Department of Physiology, University of Siena; Italy Key words: chronic fatigue syndrome, fibromyalgia, ozone therapy
SUMMARY - The aetiology of chronic fatigue syndrome (CFS) and fibromyalgia remains obscure
with a hypothetical primary infection followed by immunological, hormonal and psychological dysregula-tions. Owing to a failure of orthodox therapies, attention has recently focused on both mental and phys-ical factors although it seems certain that these diseases are not simply due to a psychological condition.
Today fairly accepted approaches are based on graded exercise therapy and cognitive behavioural therapy,but they are not always beneficial.
Several biological activities triggered by oxygen-ozone therapy performed with the method of ozonated autohaemotherapy (O3-AHT) appear suitable to correct muscle hypoxia, immune dysregulation and chronic oxidative stress. Moreover, the induction of a feeling of wellness may effectively contrast thesevere fatigue of most patients. However, orthodox medicine has neglected this approach. One goodreason is the lack of medical data and this has compelled us to report our very encouraging results in threeCFS patients and in five patients with fibromyalgia. One important observation is that therapy must notto be fixed to a rigid cycle but must be continued for several months depending upon the stage and theresponsiveness of the patient.
Nuova opzione terapeutica nel trattamento della
sindrome da fatica cronica e fibromialgia
RIASSUNTO - La sindrome da fatica cronica (CFS) e la fibromialgia rappresentano delle patologie
ad eziologia non ancora definita causate probabilmente da una ipotetica infezione primaria seguita da unaalterazione dei sistemi immunologico ed ormonale e da alterazioni psicologiche. A causa dell’insuccessodelle terapie tradizionali, è stata recentemente posta l’attenzione sui fattori fisici e mentali anche se oramaisembra accertato che la patologia non è causata solo da condizioni psicologiche. Attualmente sembrano me-todi terapeutici accettati la terapia basata sull’esercizio graduale e la terapia cognitivo-comportamentale, matali misure non risultano sempre di reale beneficio. Le molteplici attivazioni biologiche innescate dalla Ossigeno-Ozonoterapia eseguita con il metodo della autoemoterapia ozonizzata (O3-AHT) sembrano idonee per correggere l’ipossia muscolare, l’alterazione immunologica e lo stress ossidativo cronico presente in tali affezioni. Inoltre, l’induzione del senso di be-nessere può effettivamente combattere il grave affaticamento di molti pazienti. Tuttavia la medicina ufficialerifiuta tale approccio metodologico. Una buona ragione è la mancanza di dati medici e tale problema ci haspinto a riportare i nostri risultati molto incoraggianti in tre pazienti con CFS ed in cinque pazienti con fi-bromialgia. Una importante osservazione è che tale terapia non deve essere rigidamente eseguita con unoschema prefissato di cicli, ma deve essere continuata per molti mesi a seconda dello stadio e della rispostadel paziente. A Novel Therapeutic Option for Chronic Fatigue Syndrome and Fibromyalgia Introduction
menorrhea. Moldofsky et Al 18 demonstrated that adisturbance of stage 4 non REM sleep character- ized by alpha-wave intrusion into the delta rhythm bromyalgia are frustrating illnesses characterized may play a role in the development of fi- by a number of signs and symptoms among which predominate severe fatigue and a flu-like syn- The pulsatile secretion of growth hormone drome that profoundly disable patients. CFS has closely related to stage 4 sleep may therefore be- also been named chronic mononucleosis syn- come impaired with consequent decreased release drome, chronic Epstein-Barr virus (EBV) syn- of somatomedin C and muscular damage 16.
drome, myalgic encephalitis and postviral syn- It is not surprising that the following orthodox drome suggesting that the initial cause of the dis- treatments have been tested: antivirals (acyclovir, ease was believed to be a viral infection 1,2. In spite IFN alpha, immunoglobulin G), antidepressants of the fact that more than 4.000 papers have been (fluoxetine, amitryptiline, hypericum extract), anti- published on CFS 3, its aetiology and pathophysi- inflammatory drugs (a variety of cyclo-oxygenase ology remain ambiguous, but it cannot be excluded 1 inhibitors, corticosteroids) and metabolic drugs that CFS is first triggered by an undefined viral or (vitamin B12, magnesium pidolate, Q10 coenzyme, bacterial infection able to induce a chronic infec- carnitine, nicotinamide adenine dinucleotide).
tion with a concomitant immunological dysregula- They have proved to be scarcely effective and tion 4-8. Interestingly, De Meirleir et Al 9 confirmed some of them exert adverse effects 19. Prolonged Suhadolnik et Al 10 ‘s finding of an increased level rest similar to the deconditioning process occur- of 2-5 A synthetase in lymphocytes of patients with ring during ageing 20 is ineffective or harmful. On CFS. This enzyme is an excellent biomarker of an the contrary, graded exercise therapy (GET) 21,22 underlying interferon (IFN) synthesis and IFN and cognitive behavioural therapy (CBT) 23-25 ad- represents the prototypic cytokine causing a flu- ministered by specialized therapists appears to be an effective intervention for CFS patients.
However, we cannot say whether a primary in- A working group set up in 1998 to review the fection is also responsible for the disturbance of management of CFS published a report in 2001 the hypothalamic-pituitary-adrenal axis (HPA) (Report of the Working Party, 2001) 26 and has characterized by low circulating cortisol, dysregu- reached a fairly large consensus on the beneficial lated secretion of central neurotransmitters (sero- effects of GET and CBT. However, Clark et Al 27 tonin, opioids, arginine vasopressin) and growth pointed out that “none of the rehabilitation ap- hormone 13. Although the latter disturbance is con- proaches is intended to be curative, no approach troversial 14,15, it must be kept in mind because has been found to be beneficial for everyone, and growth hormone regulates the hepatic synthesis all can be tainted by poor practice by therapists and release of somatomedin C, which is a mediator lacking proper understanding of the disorder”.
of muscle homeostasis possibly implicated in Moreover, the report endorsed an additional ap- muscle pain. This aspect can be connected to the proach known as “pacing” which consists in bal- muscular alterations detected in patients with CFS16, characterized by mitochondrial dysfunc- This state of uncertainty does not help patients tion and oxidative damage documented by an in- and compels us to propose a complementary treat- creased level of 8-hydroxy-2-deoxyguanosine in ment that has been quietly performed in the last nuclear DNA and malonyldialdehyde in super- few years yielding a major, often definitive, im- provement in most CFS patients. The treatment is Relevant collateral findings have been an im- based on briefly treating the patient’s blood with paired oxygen delivery to muscle and a lower rate oxygen-ozone followed by reinfusion in the donor.
of creatinine phosphate resynthesis following high- Unfortunately, orthodox medicine is strongly bi- intensity exercise in CFS patients compared to ased towards Oxygen-Ozone Therapy despite the fact that unjustified bias is the antithesis of science.
Fibromyalgia is another obscure syndrome that We are well aware of this and we doubt that it will overlaps with CFS. In Italy, it is considered a dis- ever be contemplated in spite of having a precise ease causing considerable socio-economic prob- rationale. Indeed ozonated autohaemotherapy lems, since it affects about six million people, pre- dominantly women between the ages of 25 to 60 years. The disorder is characterized by muscu- a) improves blood circulation and oxygen de- loskeletal pain, stiffness, easy fatigability, exhaus- tion and frequent association with headache, unre- b) corrects the dysimmunity due to a possible freshing sleep, irritable bowel syndrome and dys- Rivista Italiana di Ossigeno-Ozonoterapia 1: 149-153, 2002 c) corrects the endogenous chronic oxidative draw only 100 ml of blood (either with a G 19 or stress by upregulating the antioxidant system and 21 needle) supplemented with 11 ml of Na Citrate d) induces, without side effects, a state of well- 3.8%. 100 ml of gas (O2-O3) was added (1:1 ratio) ness and euphoria consequent to the precisely cal- first with an ozone concentration of 20 µg/ml culated oxidative stress on blood (ex vivo) that acts rising to 40 µg/ml after two weeks. Ozone concen- tration was precisely checked by photometry.
A decade long period of biological and clinical Thus, the final maximal ozone dose was of 4 mg.
studies (reviewed in Bocci 28,29) completely over- After 10 min of gentle mixing, the ozonated blood looked by official medicine, support the validity of was reinfused into the donor in about 10 min. The three CFS patients received 28, 32 and 40 initialtreatments (during 3.5, 4 and 5 months, respec-tively) followed by three months’rest. After this Patients and Methods
period, we suggested resuming therapy if neces-sary.
Owing to the limitation of recruiting patients Four of the five fibromyalgia patients received this is an open, preliminary trial where patients are between 24 and 36 treatments depending upon the compared to those without treatment. The diag- response to Ozone Therapy. As Loconte previously nosis of CFS was made on the basis of the defini- reported 32 we performed careful infiltration of 5 tion of the disease made by the US Centers for Disease Control and Prevention 30. This includes of the tender sites and trigger points, alternatively.
the manifestation of several physical symptoms All patients throughout the therapy were advised such as severe fatigue during the last six months to supplement their daily diet with vitamin C (0.5 and at least four of the following symptoms: 1) sore mg), n-acetyl-cysteine (0.6 mg) and a multivitamin throat, fever, muscle pain, multi-joint pain, fre- tablet (RD doses) including vitamin E, selenium quent headaches, unrefreshing sleep, impaired memory and post-exertional malaise. The Britishcriteria 31, that insist on the presence of mental fa- Biochemical determinations: before starting the tigue, was also taken into consideration.
therapy, we tested the total antioxidant capacity The study population consisted of three patients (TAS) of the patient’s plasma. Levels ranged with CFS (one man: age 47 and two women: age 51 within normal levels (1.3-1.8 mM). Occasionally and 55) and five patients (one man and four we tested the TAS level after ozonation and we women: mean age 51.5 ± 2.3 years) with fi- found that it was decreased by no more than 10%.
bromyalgia. In this case, the diagnosis was made if Peroxidation levels (TBARS) barely increased at least 11 of the 18 tender points designated by the with an ozone concentration of 20 µg/ml but they American College of Rheumatology, elicit pain were significantly increased after 40 µg/ml to indi- when pressed. These patients reported easy fatiga- cate an effective reaction. As a further proof, a 20- bility, muscle weakness, sleep disturbance and two 30% of protein thiol groups were oxidized.
Haemolysis always remained at negligible (0.1- Pressure over tender sites very often elicited 0.4%) levels. These tests described elsewhere 29 considerable but transitory pain. All of these pa- make sure that ozone has indeed reacted with tients had suspended medical treatments for at least three months. A few patients with depressivedisorders taking antidepressants and other drugswere excluded. Before Ozone Therapy, patients were informed that the treatment was experi-mental but it had a rational basis and did not yield The weakness of our work is due to the very toxic effects. All patients signed a specific informed limited number of patients. However, the compli- ance was excellent and only one dropped out during treatment: as the patients slowly found (monday and thursday or tuesday and friday). The benefit, they were enthusiastic to continue the therapy. Of the three CFS patients, most of the 3-AHT treatment in several pathologies has been repeatedly approved by the Ethical Com- symptoms decreased after 3.5 and 3 months, re- spectively of continuous therapy. All of them were This was performed with an atoxic, optimized and felt practically normal six months after the ini- procedure using glass flasks under vacuum (no tial treatment. No side effects were reported and plastic autotransfusion bag!) as described in the all of them experienced a feeling of renewed en- appendix 29. We have been very cautious and with- A Novel Therapeutic Option for Chronic Fatigue Syndrome and Fibromyalgia Of the five fibromyalgic patients, four showed a placebo (single autotransfusion or only oxy- definitive improvement after six months whereas genated blood) would be interesting, but these pa- one woman had very poor venous access and com- tients are severely distressed and randomisation plained of blood extravasation. After four treat- ments she was dissatisfied and dropped out. We A few observations ought to be kept in mind for suggested trying rectal insufflation of O2-O3 but the future. Our schedule and the volume of blood she did not accept. The problem of difficult venous exposed to O2-O3 may not have been optimal be- puncture is rare but is real and now we can pro- cause the clinical improvement has progressed pose the option of quasi-total body exposure to slowly. While we are insisting 29 on the validity of O2-O3 that is not invasive and quite practical 34.
the strategy “start low, go slow”, we may have been During the therapeutic session we take care to talk to the patient and explain the various biological ef- The schedule of two treatments per week ap- fects resulting from the interaction of blood with pears valid and well accepted by patients but while ozone. Most of the patients appreciate the conver- we should start with a 100 ml volume of blood and sation and we believe that this is part of the treat- an ozone concentration of 20 µg/ml, during a four ment. What its relative role is in comparison to week period, we should escalate the blood volume Ozone Therapy remains to be clarified.
to the maximum of 225 ml and an ozone concen- Finally, the infiltration of O2-O3 in both tender tration of 40 µg/ml. It also appeared clear that a and trigger points of fibromyalgic muscles de- priori we cannot fix a number of treatments (say 12 serves a comment. Although they cause a transi- or 16 to be performed in 1.5 or 2 months) because, tory (3-5 minutes) pain, they usually elicit a diffuse understandably, each patient responds differently analgesic effect after 5-8 infiltrations repeated to the therapy. In our case, among CFS patients, we noted one slow, one medium and one rapid re-sponder. Consequently, we must adjust the cycleand maintenance therapy to the single patient and Discussion
not to a fixed, meaningless scheme. This is an as- Standardized medical care (antidepressants, glu- pect that ought to be extended to other patholo- cocorticoids, immunotherapy and metabolic drugs) is scarcely beneficial and with some side effects in In the case of fibromyalgia, our statistics are CFS patients. Although GET 21,22 and CBT 23-25 ap- very meagre compared to those reported by Lo- pear to represent an effective intervention, they do conte 32 and Cosentino et Al 33. The latter group de- not entirely solve the problem of two similar syn- termined a complete response in about 40% of pa- dromes that are likely due to a number of patho- tients while Loconte 32 claimed to achieve total re- genetic factors. During the last seven years of clin- mission in 60% of patients. In our case, four pa- ical experimentation in vasculopathic and in age- tients had an excellent response and this is most likely due to our far longer treatment schedule.
The direct infiltration of tender sites and trigger points can be compared with the “chemical well being and euphoria. This result is interesting acupuncture” 29 performed in the paravertebral and we can only speculate that the reasons for muscles for the problem of backache and is inter- these positive effects are due to a functional preted to activate the anti-nociceptive system via restoration of hormonal and neurotransmitter the descending analgesic neuronal complex. It may functions. Why not then try the “therapeutic be interesting to evaluate the local infiltration of a shock” of O3-AHT in patients plagued by fatigue small volume of ozonated blood that may lead to a and depression? Moreover, Ozone Therapy may complete normalisation of nociceptors. As we are change the vicious circle due to a chronic oxidative opening a Regional Ozone Therapy Center at the stress and deranged muscle metabolism. The clin- University Hospital in a few months, we hope that ical results so far obtained appear to justify the use we will be able to recruit more patients and extend of ozone in this frustrating pathology. It is worth noting that Ozone Therapy is effective because it isable to activate simultaneously several metabolicpathways that have gone astray. This also explainswhy CBT 23-25, that certainly involves the psycho-neurohumoral system, is somehow more effectivethan using single conventional drugs. Obviously, Acknowledgements
our data need to be expanded and compared with We acknowledge linguistic revision by Mrs. Helen Carter and a group of patients treated with CBT. The use of a careful editorial work by Mrs. Patrizia Marrocchesi.
Rivista Italiana di Ossigeno-Ozonoterapia 1: 149-153, 2002 References
1 Swartz MN: The chronic fatigue syndrome - one entity or 20 Degens H: Age - related changes in the microcirculation of many? New England J Med 319: 1726-1728, 1988.
skeletal muscle. Adv Exp Med Biol 454: 343-348, 1998.
2 Cope H, David A et Al: Predictors of “postviral” fatigue.
21 Fulcher KY, White PD: Randomized controlled trial of graded exercise in patients with chronic fatigue syndrome.
3 Joyce J, Rabe-Hesketh S, Wessely S: The example of chronic fatigue syndrome. JAMA 280: 264-266, 1998.
22 Powell P, Bentall RP et Al: Randomized controlled trial of 4 Caligiuri M, Murray C et Al: Phenotypic and functional patient education to encourage graded exercise in chronic deficiency of natural killer cells in patients with chronic fa- fatigue syndrome. BMJ 322: 1-5, 2001.
tigue syndrome. J Immunol 139: 3306-3313, 1987.
23 Sharpe M, Hawton K et Al: Cognitive behavior therapy for 5 Landay AL, Jessop C et Al: Chronic fatigue syndrome: clin- the chronic fatigue syndrome. A randomized controlled ical condition associated with immune activation. Lancet 24 Deale A, Chalder T et Al: Cognitive behavioral therapy for 6 Morrison LJA, Behnan WMH et Al: Changes in natural chronic fatigue syndrome. A randomized controlled trial killer cell phenotype in patients with postviral fatigue syn- drome. Clin Exper Immunol 83: 441-446, 1991.
25 Prins JB, Bleijenberg G et Al: Cognitive behaviour therapy 7 Konstantinov K, von Mikecz A et Al: Autoantibodies to nu- for chronic fatigue syndrome: a multicentre randomized clear envelope antigens in chronic fatigue syndrome. J Clin 26 Report of the working Party on CSF/ME to the Chief Med- 8 Komaroff AL, Buchwald DS: Chronic fatigue syndrome: an ical Officier for England and Wales. London: Department update. Annu Rev Med 49: 1-13, 1998.
9 DeMeirleir K, Bisbal C et Al: A 37 kDa 2-5A binding pro- 27 Clark C, Buchwald D et Al: Chronic fatigue syndrome: a tein as a potential biochemical marker for chronic fatigue step towards agreement. Lancet 359: 97-98, 2002.
syndrome. Am J Med 108: 99-1105, 2000.
28 Bocci V: Biological and clinical effects of ozone. Has ozone 10 Suhadolnik RJ, Peterson DL et Al: Biochemical evidence therapy a future in medicine? British J Biomed Sci 56: 270- for a novel low molecular weight 2-5A -dependent Rnase L in chronic fatigue syndrome. J Interferon Cytokine Res 29 Bocci V: Oxygen-Ozone Therapy. A critical Evaluation.
Kluwer Academic Press, London, England, 2002.
11 Bocci V: Possible causes of fever after interferon adminis- 30 Fukuda K, Straus S et Al: The chronic fatigue syndrome: a tration. Biomedicine 32: 159-162, 1986.
comprehensive approach to its definition and study. Ann 12 Bocci V: Central nervous system toxicity of interferons and other cytokines. J Biol Regul Homeost Agents 2: 107-118, 31 Sharpe M, Archard LC et Al: A report-chronic fatigue syn- drome guidelines for research. J R Soc Med 84: 118-121, 13 Parker AJR, Wessely S, Cleare AJ: The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psycholog- 32 Loconte S: La sindrome fibromialgica primaria. Proceed- ings I Congresso IMOS, Italia, Siena: 40, 2-4 novembre 14 Allain TJ, Bearn JA et Al: Changes in growth hormone, in- sulin, insulin-like growth factors (IGFS), and IGF - binding 33 Cosentino R, Manca S et Al: Efficacia dell’Ozonoterapia protein - 1 in chronic fatigue syndrome. Biological Psychi- nella sindrome fibromialgica. Proceedings I Congresso IMOS, Italia, Siena: 30, 2-4 novembre 2000.
15 Cleare AJ, Sookdeo SS et Al: integrity of the GH/IGF 34 Bocci V, Borrelli E et Al: Quasi-total body exposure to an system is mantained in patients with chronic fatigue syn- oxygen-ozone mixture in a sauna cabin. Eur J Appl Physiol drome. J Clin Endocrinol Metabolism 85: 1433-1439, 2000.
16 Fulle S, Mecocci P et Al: Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis ofchronic fatigue syndrome. Free Rad Biol Med 29: 1252-1259, 2000.
17 McCully KK, Natelson BH et Al: Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clinical Science 97:603-608, 1999.
18 Moldofsky H, Scarisbrick P et Al: Musculoskeletal symp- toms and non-REM sleep disturbance in patients with “fi- brositis syndrome” and healthy subjects. Psychosomatic 19 Reid S, Chalder T et Al: Chronic fatigue syndrome. BMJ

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