Additional Table 6: Orthopedic indications for O3 therapy

Concentration and

route of O3

Study Pathology administration Type of study Measured parameter(s) Results Side effect(s) Mechanism of action
Steppan et Herniated lumbar discs Intradiscal and Meta -analysis Meta -analysis for pain levels Significant mean improvement of 3.9 Significantly low Redox capabilities allow proteoglycans in the

al.
64
; Paoloni extradiscal (n = 12) (visual analog scale) complication rate nucleus pulposus to be oxidized, leading to a

et al.
65
; Oder injection (1 –3 mL Meta -analysis Significant mean improvement of 25.7 (0.064%) small decrease in volume of the nucleus
O2
for
et al.
66
; /O3)
functionality (ODI)
pulposus. Decreased volume decreases
Meta
Magalhaes et pressure and attenuates pain. O3’s
67 -analysis for Likelihood of showing improvement was anti-inflammatory effects due to the redox
79.7%
al.
functionality (modified properties are also speculated to have
MacNab) analgesic effects. O3’s disinfectant properties

are beneficial when using intra- and

extradiscal injections because it lessens the

risk of infection

Al- Jaziri et Spine and joint Intra-articular and Prospective Pain level after 4, 8, and 12 Significantly decrease ( P = 0.005, P = 0.005, None Ability to activate enzymes catalyzing peroxide
68
al. osteoarthritis paravertebral study ( n= sessions P = 0.0043, respectively) reactions allowing for protection against ROS

muscle injections 220) Follow-up pain levels (mean P = 0.0048)

Significantly decrease ( and peroxides. O3’s anti-i nflammatory,
(20 μg/mL) up time is ~10
follow- analgesic effects, and anti-oxidative effects,

months) taken together with the significantly decreased

pain levels long- term, allows for speculation

on possible histological changes after using O3

therapy

Bonetti et al.
69
First degree CT- guided bilateral Prospective Pain levels after treatments 15 patients (83.3%) had complete remission of None By injection, the gas mixture directly proximal
spondylolisthesis and periganglionic study ( n = 18) using modified MacNab pain. 3 patients (16.7%) had poor levels of to the lysis points allows for analgesic and

spondylolysis infiltration of improvement anti-inflammatory actions on the meningeal

O2-O3 and O2- O3 Pain levels at 1-month 15 patients (83.3%) had complete remission of branches of a spinal nerve. Also, prostaglandin
injection into lysis and cytokine levels are balanced because of
follow-up using modified pain. 3 patients (16.7%) had poor levels of
point of neural
MacNab improvement O3 ’s ability to increase SOD production and to

arch ¾ mL O2-O3 reduce ROS. Local improvement in circulation

gas mixture at 25 Pain levels at 3-month follow 13 patients (72.2%) had complete remission of after treatment allows for increased eutrophic
μg/mL) up using modified MacNab pain. 2 patients (11.1%) had satisfactory levels delivery
of improvement of pain. 3 (16.7%) patients
had poor levels of improvement
Pain levels at 3-month follow 13 patients (72.2%) had complete remission of
up using modified MacNab pain. 2 patients (11.1%) had satisfactory levels
of improvement of pain. 3 patients
(16.7%) had poor levels of improvement

Note: O3: Ozone; O2 : oxygen; ODI: Oswestry Disability Index; CT: computed tomography; ROS: reactive oxidative species; SOD: superoxide dismutase.