Pharmacodynamic characteristics
The data from the studies show that the components of the preparation OZONE FACTOR improve the function of cardiovascular system, reduce the effects related to the aging process, they have anti-cancer effect as well as anti-inflammatory and anti-oxidant effect.
Experimental pharmacology
Anti-inflammatory and anti-oxidant effect
In was proven in the animal models that OZ improves the circulation of the blood, the inlet of ischemic tissues. The large number of studies showed evidence that the correlation of chronic oxidant stress, caused by the growth of anti-oxidant enzymes with application of ozone causes the differentiation of erythroblasts. This results in progressive increase of erythrocytes and it is a precondition to make them resistant to oxidant stress, a process known as “oxidant preconditioning”. Ozone increased the levels of prostacyclin (known as vasodilator) of laboratory animals. Effects on cardiovascular system The data of experimental studies conducted on different animal models of atherosclerosis, hypertension, hypercholesterolemia supports the connection between oxidant stress and endothelial dysfunction. Polyphenols of olive oil contributed to the growth of concentration of nitrogen monoxide in experimental animals and prevented the creation of potent oxidant agent peroxinytrate (Perona et al. 2006), on the other hand, phenols lower the homocysteine and hence the adhesive potential of endothelium.
Effects on the aging process
In the large number of animal models, the beneficial effect of the prophylactic application of OZ treatment was proven by reducing the oxidant stress affect and aging process. It was established that the application of low dose of OZ has positive effect and alleviates the changes of the heart and hippocampus which are caused as a consequence of aging of rats. Additional studies showed that the OZ treatment may possibly influence the mechanisms included in establishing balance of deregulated redox aging potential. With rats, a reduction in the markers of oxidation of lipids and proteins was noticed, as well as reduction of deposition of lipofuscin, normalization of the levels of glutathione and normalization of GPx of the old heart tissue. At the same time, OZ reduced the energetic stifling of the heart and the hippocampus of rats which appears to be related to the aging process. The scientists suspect that the noticed improvement is due to the increasing of calcium in cytoplasm of heart cells as well as restoration of the weak Na+/K+-ATPase activity of the heart and hippocampus.
Clinical pharmacology
Effects on cardiovascular system
All conducted prospective studies showed the beneficial effect of the nutrition rich in olive oil on the total health, especially on the cardiovascular system. Epidemiologic studies showed that Mediterranean manner of nutrition (rich in virgin olive oil) reduced the risk of cardiovascular malfunctions through improvement of the main risk factors of cardiovascular diseases as lipoprotein profile, blood pressure, metabolism of glucose and anti-thrombotic profile. The positive modeling is applied on the endothelial function as well, on the level of inflammation and oxidant stress. In the different studies conducted on people, it was noticed that the consumption of meals with olive oil rich with phenol composition improves the function of endothelium of postprandial period (Vogei et al. 2000; Karatzi et al. 2008; Fuentes et al. 2008; Ruano et al. 2007). The largest studies are conducted in the countries of South Europe. The association between the intake of olive oil with the reduction of death risk of any reason and death risk of specific reason was conducted on Spanish population and hence the largest reduction of cardiovascular death reduction was noticed (44% risk reduction conducted together with people that did not consumed olive oil). It was noticed that the gradual increase of the intake of olive oil was connected with decreasing of the risk of cardiovascular death (increase of 10 g of 2000 kcal resulted in decrease of the risk by 13%) (Buckland et al. 2012). In two newer prospective studies also about the association between the intake of olive oil and incidents of coronal diseases, the significant reduction of the cardiovascular risk was registered (-44%) in the comparison with the quarters with the largest daily intake of olive oil compared with those with the lowest intake of olive oil (>31,2 g/d compared to ≤15 g/d – Italian study EPICOR) (Bendineli et al. 2011); lower reduction of risk (-22) of massive consumers (>28.0 g/d) was noticed by the Spanish cohort study (Buckland et al. 2012). In the three studies conducted in France, the participants intensely consumed olive oil and they had by 41% lower risk of insult, compared to those who never used it (Samieri et al. 2011). It is known that the cerebral vasospasm after subarachnoid hemorrhage is one of the key factors that make the rehabilitation of the patient harder. In one animal model, the effect of intervening therapy with OZ was tested on the vasospasm of the femoral artery of rats. The results of histopathological and morphometrical analysis showed that the treatment with OZ reduced the morphometrical changes, malfunctions of endothelium and haemorrhaging as a result of vasospasm. These notions show the anti-oxidant and anti-inflammatory effects of OZ and the potential use of OZ as a therapy for posthaemorrhagic vasospasm.
Anti-inflammatory and anti-oxidant effect
Effects on the aging process
Additional studies were conducted to people for testing the beneficial effect of ozone therapy as OZ-ANT in combination with Q10 applied orally. This research showed the levels of the potent antioxidant SOD and catalase activity in the controlled group of participants and two active groups that took either only ozone or ozone in combination with Q10. The results showed significant increase of SOD and insignificant increase of catalase activity in O3 + Q10 conducted with control. At the same time, at O3 + Q10 group, significant decrease in concentration of malondialdehyde was noticed (product of lipid pre oxidation and indication or oxidant damaging of cell membranes). In random study in vivo, the change of expression of genes in mononuclear healthy volunteers was evaluated after intake of olive oil with high and low content of phenols. Significant change in the genetic expression was noticed related to inflammation and oxidant stress between the group that used olive oil and the controlled group. At the same time, significant linear decrease regarding the content of phenols of oil in the genetic expression was established as a response to inflammation. (interferon gamma, Rho-GTPase activating protein 15) and oxidant stress (adrenergic beta 2 receptors).
Effects on the process of aging and Alzheimer disease
Micro constituents present in the virgin olive oil showed antioxidant properties and capacity for improvement of the function of endothelium of people. Additionally, modification of homeostasis and anti-trombosclerotic effect was noticed. Different observatory studies conducted to people showed that the intake of unsaturated fats has protective role against the decrease of cognitive functions due to aging or Alzheimer disease. The scientists from Lewiz Katz, the school of medicine at the Temple University published a study in the journal Annals of Clinical and Translational Neurology. They emphasize the notion that the extra virgin olive oil reduces the formation of beta-amyloid plaques and neurofibrillary tangles – classical indicators of Alzheimer disease. In another study, Prof. Domeniko Pratiko with his team discovered some mechanisms that prove the protective properties of olive oil. The active substances of olive oil reduce the inflammatory processes of the brain and activate autophagy process. The mice, that consumed extra virgin oil, had an increased level of authophagy in the brain cells and a decreased level of amyloid plaques and hyperphosphorylated tau-protein responsible for neurofibrillary tangles that contribute to dysfunction of nerve cells and are associated with the appearance of Alzheimer diseases. The animals were divided to two groups and in the end of the study huge differences were noticed in the appearance and the functions of brain cells, i.e. synaptic connections were better preserved by mice that consumed olive oil and the process of authophagy was increased in them. By the active group of experimental animals, better memory and learning ability was noticed.
Anti-cancer effect
The virgin olive oil contains many nutrients that are proven antioxidants, hence it is considered to have anti-cancer properties. The results of several studies conducted in Spain proved that the olive oil has beneficial effect to patients with breast cancer. Antioxidant polyphenols, contained in the cold-pressed olive oil decrease the activity of the gene HER2, which is associated with the development of breast cancer. Dr. Javier Menendez from the Catalan Institute of Oncology and Dr. Antonio Segura Carretero from the University of Granada, in their research of the most-efficient anti breast cancer ingredients, established that the quality unrefined olive oil contains a large number of “phytochemical” ingredients that cause the death of malignant cells. Oleic acid, as a main component of olive oil, bclocks the activity of oncogenes HER-2/neu, which were discovered in 30% of the patients with breast cancer and stir the development of malignant cells.
The use of traditional medicine
The healing properties of the oil are well known since the ancient times. In the traditional medicine, the olive oil is used for its positive influence on the immune defense of the body, detoxification, establishment of energetic balance, reduction of cholesterol level, prevention of cardiovascular diseases, normalization of blood pressure. The olive oil is regularly used as a traditional cure for burns, seborrhea, pigmented marks, insect bites as well as for healing of skin ulcers in the form of heated pads. The virgin olive oil is traditionally used in the treatment of biliary calculi. The oil stimulated in the natural way the treatment of gall-bladder and easier removal of calculi present in the biliary gallbladder and gallbladder duct. Some people use olive oil as a natural preparation for enema when intestines or stomach are inflamed, for optimization of the digestive system, for healing of hemorrhoids that are bleeding, as a cure for slow-moving stiff joints. Besides the olive oil, the olive leaf is used in traditional medicine as well, which is recommended in today’s herbal pharmacies (in the form of tea) to people with increased level of sugar in the blood (diabetes). Since the 19th century, the ozone is used for treatment of different conditions such as immune system regulation, improvement of cell metabolism, regulation of lipids metabolism and circulation improvement, alleviation of headache symptoms, different neurological malfunctions, decreasing of negative effects of smoking, hormonal status balance, circulation improvement. Its use in the conditions of exhaust, insomnia, energy deficiency, concentration problems and chronic fatigue is well-known.
Toxicological characteristics
There are limited data regarding the toxicological characteristics of the components of the preparation. The limited data and the results of the published studies as well as the safety pharmacology of the components of the preparation indicate accepted toxicity of the OZONE FACTOR for the general population.
Clinical safety/pharmacovigilance
The analysis of the results from the conducted clinical studies regarding the safety of olive oil enriched with ozone, the experience from the past use as well as the literary data for the product OZONE FACTOR indicate an acceptable safety profile of the preparation and an absence of serious unwanted effects from its use in the recommended doses. When using the ozone, there is an appearance of allergic reaction, bleeding (mostly to people with coagulation problems), convulsions (due to the stimulating effect on the central nervous system) registered. The large amount of ozone irritates the respiratory system, the mucous membrane of the eyes, the eye canals, hence the flow of tears is registered, which can cause cataract as well as immune system diseases. High concentrations are related to pulmonary edema, haemorrhaging and decreased exchange of gases though alveolar membranes.
The olive tree or the olive (Olea europea) is a small tree from the family of Olives (Oleaceae). It originates from the east Mediterranean parts as well as North Iran (coast of Caspian Sea). The olive tree is successful only in south, warm areas on a temperature up to 10 Celsius degrees. The first olives were cultivated almost 6000 years ago and since then, they are highly-appreciated in the nutrition, medicine and cosmetics.
The fruit of the olive is mostly consumed. It is eaten raw or conserved, but the popularity of the olives is related to the oil as well, which is obtained from the fruit and due to the beneficial characteristics on health, it is called “Mediterranean gold”.
The fruit of the olive contains around 35% oil. The quality olive oil has sweet-bitter flavour, greenish colors and fruit odor. The hard odor of the olive oil is a sign that it is not quality and it is old oil.
There are 3 types of olive oil:
-Virgin olive oil (olio vergine) – the healthiest and the most quality olive oil, obtained with the first cold-pressing of healthy olives, whereby the olive pit should not be squashed. In this procedure, heating is not used, only the so-called procedure of “cold-pressing” is allowed. The virgin olive oil contains below 1% of free fatty acids. Nutritionists consider the extra-virgin olive oil to be exceptionally healthy food, rich with chlorophyll, carotene, lecithin (natural anti-oxidant that stimulates the metabolism of fats, carbon-hydrates and proteins), polyphenols (anti-oxidants) and essential vitamins D, E and K.
-“Provence” oil obtained its name after the south-east area of France, which is the place of its origin. It is the second quality oil. With its extraction, the olive pits are squashed, but heating is not used in this procedure as well.
-“Wooden” olive oil – is an oil with the lowest quality. It is obtained by additional extraction of the residues after the production of the “provence” oil using heat. The oil obtained in this way is mostly used for production of soaps and technical oils.
The olive oil is rich with unsaturated fatty acids, including oleic acid, palmitic acid and linolenic acid. Moreover, the virgin olive oil contains phenolic antioxidants as active compounds including pure phenols, aldehyde secoiridoids, flavonois and lignans.