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; ItalyKey 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 dellaautoemoterapia ozonizzata (O3-AHT) sembrano idonee per correggere l’ipossia muscolare, l’alterazioneimmunologica 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 FibromyalgiaIntroduction
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
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