FATIGUE AND SPORTS: WHAT ARE THEY?
Fatigue is an asthenic-depressive syndrome that affects cancer patients both during and after therapeutic treatment. This syndrome is multifactorial and is due to factors that are not only psychological but also organic in nature. The main pathogenetic mechanisms of organic nature are related to the side effects of chemotherapy. Genotoxic anticancer drugs, such as cisplatin, 5-fluorouracil, anthracyclines, and nitrosoureas, affect not only the nuclear DNA of cycling cells but also the mitochondrial DNA of stable and perennial cells, including skeletal muscle and neuronal cells. Mitochondrial DNA is continuously replicated even in differentiated cells blocked in the G0 phase of the cell cycle. In fact, the mitochondrion has a mitotic replication cycle every 20 days; this mitochondrial mitosis is independent and autonomous from the replication of the cell that hosts it. Mitochondrial DNA is much more sensitive to genotoxic damage than nuclear DNA. This fragility is due to the following mechanisms: (a) lack of histone packaging; unlike nuclear DNA, mitochondrial DNA consists of a circular double helix filament of 16,562 base pairs completely exposed to binding with genotoxic agents; (b) lack of effective DNA repair systems; (c) lack of redundancy mechanisms in the genetic code, making the mitochondrion one of the very few exceptions; this situation means that mutations in the second and third base of the triplet, normally inconsequential for amino acid synthesis due to genetic code redundancy, instead in the mitochondrion cause amino acid substitution and therefore mutation. For these reasons, after chemotherapy, mitochondria in skeletal and cardiac muscle dramatically decrease in number and functionality. In skeletal muscle, this situation leads to the onset of the asthenic syndrome known as ‘fatigue’. Astenia and consequent physical inactivity have important direct repercussions on mood tone. In fact, physical activity leads to the production of endorphins, which help maintain an individual’s sense of well-being and keep mood tone high. In the absence of this situation, in cancer patients, mood tone is typically altered with the onset of depressive
symptoms. This situation can be countered by the administration of adapted physical activity, which represents a proven measure capable of reducing the risk of cancer recurrence by 40% and alleviating or preventing fatigue. However, not all cancer patients are able to perform adapted physical activity. It is, therefore, necessary to develop a category of dietary supplements capable of pharmacologically activating the mechanisms activated by physical activity. These supplements are defined as ‘physical-activity mimicking drugs’. They must be characterized by high compliance, very low or no toxicity, and ease of administration. Among the emerging molecules in this category, ozone oils with high ozonides stand out for their interest and practicality of use. These supplements are administered orally in the form of gastro-resistant capsules and are virtually free of side effects. They are composed of oleic and linoleic acid complexed with ozone through stable ozonide bonds. Oleic and linoleic acids are two essential oils necessary for the body’s physiology, normally ingested through diet. Ozone is an allotropic state of oxygen. The lipophilic carrier (oleic and linoleic acid) allows ozone to enter cells capable of catabolizing lipids. Among these, cells rich in
mitochondria stand out, such as striated muscle cells, which produce most of the ATP needed for acto-myosinic contraction through beta-oxidation of fatty acids. Intracellular fatty acid catabolism breaks the ozonide bond, releasing oxygen and a minimal amount of reactive oxygen species. The release of oxygen generates increased availability of this gas intra-tissue, resulting in a 30% increase in aerobic threshold after just one week of treatment. Note that at least 3 months of physical activity are usually required to achieve this result. The minimal amount of reactive oxygen species released in normal cells is easily countered by antioxidant defences, which are, in fact, activated by them through the hormesis
mechanism. On the contrary, in surviving neoplastic stem cells, these reactive oxygen species scavenge antioxidant species, contributing to reducing the risk of recurrence and the onset of chemo-radioresistance.
The increased availability of oxygen has direct effects on improving asthenia, which also reflects on the improvement of mood tone. So far, about 300 oncological patients have been treated, observing an almost constant improvement in mood tone, which worsened upon discontinuation of the supplement but improved again upon resumption of treatment (cross-out evaluation). Ozone is a well-known anti-inflammatory agent. The inhibition of macrophage oxidative burst exerted by ozonized oil is relevant to attenuate the inflammation surrounding and penetrating the tumour tissue by modulating tumour-associated macrophages that contribute to cancer development.
The release of oxygen inside solid cancer is crucial to counteract neo-angiogenesis and metastatic spread. Indeed, hypoxia triggers (a) the production and release of angiogenic factors by activating Hypoxia Inducible Factor 1; and (b) metastatic spread by activating the met oncogene. It should be noted that these effects are obtained only from oils with a high ozone load in terms of ozone content.
For the reasons outlined, ozonized oils with high ozone content administered orally seem to represent an interesting opportunity for improving the quality of life in oncological survivors.
Bibliography:
[1] Izzotti A., Fracchia E., Rosano C., Comite A., Belgioia L., Sciacca S., Khalid Z., CongiM., Colorassi C., Blanco G., Santoro A., Chiara M, Pulliero A. Efficacy of high-ozonide oil in prevention of cancer relapses. Mechanisms and clinical evidence. Cancers 2022, 14,1174-1198.
[2] Izzotti A, Fracchia E, Au W, Colombo M, Pfeffer U, Emionite L, Pavan S, Miotto D, Lova P, Grasselli E, Faelli E, Ruggeri P, Tiso M, Pulliero A. Prevention of Covid-19 infection and related complications by ozonized oils. J pers. Med. 2021, 11, 226-242
[3] Semenza GL. Hypoxia-inducible factor 1 and cancer pathogenesis. IUBMB Life 2008, 60, 591-7.
[4] Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003, 3, 347–61.
FATIGUE AND SPORTS: DOSAGE
METHOD OF USE:
CAPSULES O3ZONE SIZE 00
4 CAPSULES PER DAY
MINIMUM DURATION 60 DAYS (physically active)
(2 in the morning and 2 in the evening)
CAPSULES O3ZONE SIZE 00
6 CAPSULES PER DAY
MINIMUM DURATION 60 DAYS
(physically inactive due to health issues)
(3 in the morning and 3 in the evening
ADMINISTRATION METHOD:
ENTERIC-COATED CAPSULES FOR SYSTEMIC USE ORALLY
TREATMENT DURATION:
2-3 MONTHS
EXCLUSION CRITERIA:
Pregnant women
Internal and external bleeding
Surgical interventions (suspend treatment 3 days before and resume 7-10 days after)
Hyperthyroidism
Favism
TREATMENT OBJECTIVE:
The objective of the integrated treatment is to increase the amount of oxygen at tissue and cellular levels, thereby increasing the aerobic threshold.
Recommended as integrated therapy:
For chronic fatigue and in sports activities.
ROLE OF OZONE IN THE TRANSPORT AND UTILIZATION OF OXYGEN IN OXIDATIVE METABOLISM
The aerobic system is an energy system that utilizes fats, carbohydrates, and sometimes proteins for ATP (adenosine triphosphate) synthesis, a molecule present in all living organisms as a slower energy accumulation form. Therefore, it is not capable of fueling the body during VERY INTENSE exercises, which require rapid ATP production.
The positive effects are numerous:
1) Increase in the volume of mitochondria;
2) Increase in oxidative phosphorylation of ATP;
3) Increase in capillarization and pulsatory flow;
4) Improvement in myocardial contractility;
5) Enhancement of cerebral glucose metabolism.
Through its antioxidative mechanism, Ozone counters the ablation of free radicals, reactivates the microcirculation, and INCREASES the deformability of red blood cells, resulting in an increase in oxygenated haemoglobin concentration and an elevation in the required ATP.