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Book: Sports Nutrition and Health. From Nutrients to Performance
Sports Nutrition and Health. From Nutrients to Performance
Location: Germany
Author(s): Maricela Dragomir
Title: OZONE THERAPY AS A CRUCIAL ADVANTAGE FOR TOP-PERFORMANCE ATHLETES:
EXPLORING ITS ROLE IN METABOLIC REGULATION AND THERAPEUTIC OUTCOMES
OZONE THERAPY AS A CRUCIAL ADVANTAGE FOR TOP-PERFORMANCE ATHLETES:
EXPLORING ITS ROLE IN METABOLIC REGULATION AND THERAPEUTIC OUTCOMES
URL: https://www.ceeol.com/search/chapter-detail?id=1307365
CEEOL copyright 2025
20. OZONE THERAPY AS A CRUCIAL
ADVANTAGE FOR TOP-PERFORMANCE
ATHLETES: EXPLORING ITS ROLE
IN METABOLIC REGULATION AND
THERAPEUTIC OUTCOMES
Maricela DRAGOMIR
“Dunarea de Jos” University of Galati, Romania
Abstract
Ozone therapy has developed over the last 150 years. Initially used to
disinfect drinking water, ozone has demonstrated its usefulness in
combination with oxygen as a complementary therapy with broad
appeal and few contraindications. However, some controversies
still require further studies, most of them related to the toxic effect
of ozone inhalation on the lungs. The effects of ozone therapy
are dose-dependent and on individual oxidative status. The
action mechanism of ozone is determined by concentration. The
therapy has analgesic, immunomodulatory, anti-inflammatory,
antibacterial, antiparasitic, antifungal, and virostatic effects. By
increasing mitochondrial energy production, ozone therapy could
be recommended as a primary way to prevent and combat muscle
fatigue. Research and clinical case reports show positive results
in treating musculoskeletal, neurodegenerative, cardiovascular,
metabolic, dermatologic, digestive, and other conditions. Having
a steroid-like effect, ozone therapy can be used mainly to reduce
inflammation and pain. As a safe procedure, in compliance with
current protocols and the World Anti-Doping Association Code,
ozone therapy can be recommended to top-performance athletes
for recovery after physical exertion, injury or illness.
Keywords
Ozone therapy; Recovery; Musculoskeletal disease pain; Anti-
inflammatory; Antioxidant; Anti-doping.
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1. Introduction
Ozone (O3) is an allotropic form of oxygen with three atoms in
the molecule. It is a strong, highly unstable, colourless oxidiser
with a slightly bluish tint and a specific, pungent odour [Oyama,
2000]. It is ten times more soluble in water than oxygen (O2) and
very unstable. There are several sources of ozone: atmospheric
O3 (stratosphere and troposphere), O3 produced by generators
(industrial and medical) and endogenous O3 produced in the
human body, in leucocytes and antibodies [Babior et al. 2003].
In the atmosphere, O3 is found between the stratosphere and
the troposphere, which results from the interaction of O2 with
ultraviolet B (UVB) rays and forms a protective layer. The
troposphere contains most of the O3 produced by combining
O2 with benzene-fluoro-chlorinated compounds and is toxic to
the human body [Carlisle et al. 2001]. The toxicity of O3 in the
stratosphere has raised suspicions about the safety of oxygen-
ozone therapy (OOT) [Bocci, 2007], but it represents two
different faces of the same product. O3 produced by CE- classified
medical generators, class IIb, comes from pure O2 (99.97%). It is
safe and can be dosed very accurately. OOT is a complementary,
sometimes alternative, medical procedure of administering an O2
- O3 mixture for therapeutic purposes by various routes. It has very
few, primarily relative, contraindications. OOT has a rich history,
starting in 1785 when Martinus van Marum discovered the
existence of a gas near electric machines with a destructive effect
on mercury. In 1832, Christian Friedrich Schönbein succeeded in
synthesising O3. In 1885, Dr Kenworth wrote the first manual on
the use of O3 in the medical field. In 1896, Nikola Tesla patented
the first medical ozone generator [Schwartz, 2020]. During the
First World War, doctor George Stoker treated war wounds with
a mixture of O2 - O3 [Quintero et al. 2017]. The positive effects of
OOT have been a challenge for many researchers until nowadays,
which is why medical databases contain numerous scientific papers
on this topic, many of them written in the last five years [Serra et
al. 2023]. OOT is not used to its true value, with some authors
recommending further research to substantiate the pharmacology
of O3 [Re, 2024], although the level of confidence according to
the Scottish Intercollegiate Guideline Network criteria is similar
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or superior to other procedures used in pain therapy [Hildago-
Tallon et al. 2022].
2. The action mechanism of O3
The action mechanism of O3 depends on its concentration. The
therapy has analgesic, immunomodulatory, anti-inflammatory,
antibacterial, antiparasitic, antifungal and virostatic effects. In
chronic inflammatory syndrome, due to the antioxidant system
dysfunction, there is increased oxidative stress, clinically evidenced
by impaired reduced glutathione (GSH)/ oxidised glutathione
(GSSG) ratio. Administered systemically, the treatment with
O3 in low doses, through controlled oxidative stress, has a bio-
modulatory effect [Viebahn- Hänsler and León Fernández, 2021].
O3 unlocks the antioxidant system, acting through its second
messengers (“ozone peroxides”, similar to hydrogen peroxide
– H2O2), which are redox “signalling” molecules, via the NrF2
pathway. The presence of second messengers increases the
antioxidant response system (ARE) and antioxidant enzymes
such as superoxide dismutase, glutathione-s-transferase, and
catalase. In the presence of ARE, GSH decreases oxidative
stress and proinflammatory cytokines, relieving inflammation
and pain [Viebahn-Haensler and León Fernández, 2021]. The
activation of the NrF2/ARE pathway has a protective role against
neurodegenerative diseases [Sagai and Bocci, 2011]. When
oxidative stress is severe, tissue damage occurs by increasing
proinflammatory cytokines, cyclooxygenases, and prostaglandins
through the NFkB pathway and “ozone peroxides” via leukocytes,
which produce antibodies, and achieve immunomodulation. A
third action mechanism of “ozone peroxides” is the stimulation
of erythrocyte glycolysis, with increased production of ATP and
2, 3-di-phosphoglycerate, shifting the haemoglobin dissociation
curve to the right, with increased O2 supply to the cells [Sagai
and Bocci, 2011]. In high concentrations and doses, applied
topically, O3 acts by a direct mechanism, forming reactive oxygen
species (ROS), which are bactericidal and fungicidal and have the
propriety of inactivating the viruses. In acute and chronic pain
therapy, in addition to decreasing inflammation via the NrF2/ARE
antioxidant pathway, O3 also produces oxidation of algogenic
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receptors, with immediate activation of the antinociceptive system
and a decrease in pain [Re et al. 2010].
2.1. Indications and contraindications
OOT indications belong to a wide range of conditions both in
athletes and non-athletes: cardiovascular, surgical, dermatology,
digestive, urogenital, immunological, infectious, musculoskeletal,
metabolic, neurological, endocrinological, etc. [Bocci, 1999].
Contraindications to treatment with O2–O3 fall into two categories:
absolute and relative. There is only one absolute contraindication:
deficiency of glucose-6-phosphate dehydrogenase (G-6-PDH).
Relative contraindications, in which OOT can be administered
with caution, include uncontrolled hypertension, decompensated
hyperthyroidism, psychomotor restlessness, thrombocytopenia,
haemorrhage within the last three months, and leukaemia. A
relative contraindication is the pregnancy period.
2.2. Routes of O2-O3 therapy
OOT is very flexible in terms of administration, and several routes
can be used: enteral administration, parenteral (intravenous,
intramuscular, subcutaneous, intradiscal, insufflation in rect, vagin
and bladder, transcutaneous and mucosal administration.
Respiratory administration is forbidden due to the side effects of O3
on the respiratory system [Bocci, 2007]. In athletes, administration
in the form of MAH or ozonated physiological saline is forbidden
because it involves blood manipulation, a procedure prohibited by
the World Anti-Doping Agency (WADA).
3. Ozone therapy, preventive and curative effects in sports
activity
3.1. Ozone therapy in exercise recovery
3.1.1. OOT vs nutritional supplements–anti-doping safety
Increased sports performance is determined by numerous factors,
the most important of which are physical, psycho-emotional,
nutritional, environmental, and training-related. Adequate
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nutrient intake in terms of calories and dietary principles,
together with hydro-electrolyte balance, is a major challenge. The
use of various nutritional supplements exposes the athlete to the
ingestion of substances that are sometimes defined as doping
substances in the WADA list. Thus, in the last five years, several
athletes in tennis, athletics and skating have been suspended for
doping test detection of prohibited substances, some of them
coming from contaminated food supplements [Walpurgis, 2020].
OOT can be successfully used instead of dietary supplements. The
increased need for energy is provided by the stimulation of aerobic
glycolysis of erythrocytes by O3, with the production of ATP via
the pyruvate pathway [Elvis and Ekta, 2011]. The decrease in
inflammation under the action of O3 is similar to steroidal [Serra
et al. 2023] and non-steroidal anti-inflammatory drugs [de Souza
et al. 2024].
3.1.2. Involvement of O3 in preventing and combating muscle
fatigue
Regular muscular activity (endurance exercise) consumes energy,
which the body is trained to produce from pyruvate by aerobic
oxidation via the Krebs cycle and oxidative phosphorylation.
When physical exertion is intense (prolonged weight-lifting
exercises, competitions, contact sports), the brain controls the
rapid production of ATP by anaerobic glycolysis, with lactic acid
(LA) formation. The body’s acidity stimulates the conversion of
LA into lactate, which is eliminated by several routes. The most
important pathways seem to be the production of glucose by
the gluconeogenesis mechanism in the liver or its conversion to
energy via the „lactate-alanine” cycle, which the body will use
in the striated cardiac and skeletal muscles. Extremely long or
intense physical exertion increases LA production, temporarily
exceeding the body’s ability to convert lactate, which accumulates
in the muscles. This is felt as a burning sensation in the muscles,
causing a decrease in physical performance. The same happens in
overtraining, incomplete recovery after exercise or pathological
situations. Through several mechanisms based on its antioxidant,
anti-inflammatory and blood circulation-stimulating effects, OOT
prevents LA accumulation by promoting lactate metabolisation.
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This results in rapid recovery after exercise, which is essential for
sports performance. O3 is highly unstable. Administration of O3
increases plasma O2 levels and releases active (atomic) oxygen
which, through moderately controlled oxidative stress, interacts
with molecules in the body, generating transient increases in
ROS. This increase has the effect of activating the endogenous
antioxidant system, protecting muscle cells. The increased level
of O2 in the blood improves cellular metabolism, stimulates
cellular oxidative processes with increased ATP production
via aerobic glycolysis, and balances the NADH/NAD+ ratio.
The effect of excess energy (ATP) in muscle cells is to increase
endurance and performance. Acting on vascular endothelial cells
by increasing nitric oxide (NO) production, O3 has a vasodilatory
and microcirculation-stimulating effect, accelerating the delivery
of O2 to muscle cells and recovery after intense exercise.
3.2. Cardiovascular effects of O3 use in athletes
Exposure of athletes to tropospheric O3 has adverse respiratory
and cardiovascular effects [Frampton et al. 2015], translated by
increased respiratory rate and arterial blood pressure. Exposure to
the O2 -O3 mixture is accompanied by increased oxygen delivery,
decreased platelet aggregation, vasodilation due to decreased
endothelin-1 and increased NO in vascular endothelial cells.
Another effect of OOT is the increase of renin in juxtaglomerular
cells, with a vasodilator effect, which is evident in patients with
peripheral vascular diseases and hypertensive or diabetic patients
[ Juchniewicz and Lubkowska, 2020].
3.3. Psycho-emotional and hormonal balancing
By decreasing inflammation, OOT achieves internal environmental
homeostasis and balances the neuroendocrine system. The
impact of OOT on cells decreases their resistance to insulin and
modulates insulin production in pancreatic alpha cells, affecting
glycaemic values. This decreases glucagon production. Through
its anti-inflammatory effect, OOT appears to act on ghrelin
(“hunger hormone”) and leptin (“satiety hormone”), modulating
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their activity with a response to body weight control. By regulating
oxidative status, O3 achieves neuronal protection, including in
GALP-1-producing neurons, supporting brain function. The
influence on gonadotropic hormones and sexual behaviours is
one of the roles of GALP-1. By stimulating the hypothalamic-
pituitary-gonadal axis, OOT increases gonadotropin production.
O3 exerts a normotropic effect on the hypothalamic-pituitary-
adrenal and hypothalamic-pituitary-thyroid axis, modulating
thyroid and adrenocortical activity [Nazarov et al. 2021].
3.3. OOT in injury recovery
3.3.1. Treatment of wounds
Athletes are exposed to injuries during their activities. The
most common wounds are abrasions, punctures, sunburns, and
cuts. In the case of wounds, O3 has multiple effects. Classical
surgical wound treatment remains paramount, with OOT
being complementary. The antibacterial effect is established by
flushing with ozonated water and exposing the wound in bags
with O2 - O3 gas mixture at increased concentrations, having
an antibiotic effect even on superinfected wounds. Application
of O3 in low concentrations (creams, ozonated oils, MiAH, O3
sauna, subcutaneous infiltrations, and rectal insufflations) has
anti-inflammatory and regenerative effects. Activation of PDGF
(platelet-derived growth factor), TGF-ß1 (transforming growth
factor beta 1), FGF (fibroblast growth factor), and VEGF
(vascular endothelial growth factor) gives O3 regenerative and
wound healing properties [ Junchniewicz and Lubkowska, 2020].
Simultaneously with the release of cell growth factors, cytokines
(IL 6, IL 10) and anti-inflammatory chemokines are produced
that modulate the immune response, favour pain relief and repair
of tissues damaged by trauma.
3.3.2. The effect of OOT in musculoskeletal recovery and pain
control
Performance sports involve moderate and intense physical effort.
Moderate physical exertion is beneficial to health, whereas intense
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physical exertion leads to overtraining and musculoskeletal
dysfunctions specific to each type of sport. Over time, these
dysfunctions become chronic and lead to illness. Rotator cuff
syndrome, locked shoulder, rotator cuff tendinitis, Achilles
tendinitis, bursitis, lumbar pain, carpal tunnel syndrome, and
“tennis elbow” are common and benefit from the effects of OOT.
Stimulating the production of anti-inflammatory cytokines
recommends OOT in most acute and chronic musculoskeletal
conditions, generally as a complementary, sometimes alternative
therapy with the advantage of rapidly decreasing pain, increasing
joint mobility and reducing recovery time. In knee injuries,
common in tennis players, football players, and runners, the
administration of O3 rapidly decreases inflammation and pain,
having a similar effect to hyaluronic acid [Hidalgo-Tallón et
al. 2022]. The administration of O3 in low lumbar back pain in
disco-vertebral pathology is the most frequent topic analysed by
specialists, with many “in vitro” and “in vivo” studies on this subject
[Hildago-Tallon et al. 2022; Serra et al. 2023]. Comparative
studies on the effect of OOT in lumbar disc pathology with
radicular conflict in relation to anaesthetics and corticosteroids
show an increased percentage of satisfaction, with a reduction
of the herniated nucleus in O3 [Andreula et al. 2003]. The anti-
inflammatory effect of O3, similar to corticosteroids [Serra et al.
2023], makes it preferred in tendon disorders without the risk
of rupture. It seems that O3, like other medical gases, is apt to
activate certain systems able to preserve therapeutic efficacy for a
long time [Nazarov et al. 2011].
3.3.3. OOT complementary treatment in the prevention and
treatment of neurodegenerative disorders
In athletes, particularly in contact sports, repeated minor
traumatic brain injuries are a cause of encephalopathy [Masan et
al. 2021; Pierre et al. 2022], manifested by cognitive dysfunction,
depression, neurological disorders, Alzheimer’s, or dementia.
OOT, by modulating immune response, increasing O2 delivery
to tissues, and balancing oxidative status may be indicated in
the prevention and treatment of neurodegenerative diseases
[Tahmasebi et al. 2021] and neuropathic pain [Yang et al. 2023].
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4. The effects of O3 in improving quality of life
The current concept of health is to add years to life and life to
years, increase well-being, delay ageing processes [Scassellati et
al. 2020], and increase the quality of life [Serra et al. 2023], and
OOT has this quality [Clavo et al. 2023].
5. Conclusions
Ozone can have both beneficial and toxic effects on humans,
depending on the dose and route of administration. Ground-level
ozone and inhaled ozone are harmful regardless of the dose. Ozone
therapy is a complementary procedure and can be an alternative
to conventional therapy in certain situations. Although ozone
therapy has been in use for about 190 years, and the mechanisms
of action of ozone are generally well known, it is not used to its
total value, as the respiratory toxic effects cause susceptibility.
When protocols are followed, OOT is a safe procedure without
toxic effects on the human body. Depending on the dose,
OOT has anti-inflammatory, analgesic, immunomodulatory,
antibacterial, antifungal effects and stops the growth of viruses.
Treatment with O2 -O3 gas mixture benefits from multiple routes
of administration; the choice of administration route depends on
the pathology and the desired effect. The World Anti-Doping
Association considers that ozone therapy has no doping effects
but forbids administration as major autohemotherapy because the
procedure involves blood manipulation. At high doses, applied
directly, O3 forms reactive oxygen species, destroying bacteria,
fungi, and viruses, with applicability in treating skin lesions. In
moderate and low doses, through controlled oxidative stress,
ozone acts through its second messengers (“ozone peroxides”),
balancing the antioxidant system and decreasing inflammation,
making it useful in autoimmune diseases and chronic diseases.
Ozone therapy can trigger specific mechanisms responsible
for maintaining the therapeutic effect over a long period after
completing a treatment series. The increase in mitochondrial ATP,
the stimulation of aerobic glycolysis via the pyruvate pathway
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and the effects on cellular oxygenation recommend it for use in
preventing and combating muscle fatigue in athletes. The anti-
inflammatory and analgesic effects of the O2 - O3 gas mixture
are similar to steroidal and non-steroidal anti-inflammatory drugs
and are free from their side effects. The clinical results obtained
in treating various pathologies in millions of patients justify
specialists recommending OOT in athletes.
More studies are needed on specific types of disease to develop
more accurate protocols and clarify all the pharmacological aspects
of ozone, which are a source of hesitation in recommending
ozone therapy. However, according to the Scottish Intercollegiate
Guideline Network criteria, the level of confidence in the effects of
ozone therapy is similar to or higher than that of other procedures
used in pain therapy.
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