The Oxygen-Ozone Adjunct Medical Treatment According to the Protocols from the Italian Scientific Society of Oxygen-Ozone Therapy: How Ozone Applications in the Blood Can Influence Clinical Therapy Success via the Modulation of Cell Biology and Immunity.

BACKGROUND: Ozone is an allotrope of oxygen whose use in medicine has rapidly grown in recent years. Ozonated blood allows for the use of ozone in a safe modality, as plasma and blood cells are endowed with an antioxidant system able to quench ozone's pro-oxidant property and to elicit the Nrf2/Kwap1/ARE pathway. METHODS: We present two clinical studies, a case-series (six patients) observational study adopting ozone as a major autohemotherapy and topical ozone to address infected post-surgical wounds with multi-drug resistant bacteria and an observational study (250 patients) using ozonated blood for treating knee osteoarthritis. RESULTS: Ozonated blood via major autohemotherapy reduced the extent of infections in wounds, reduced the inflammatory biomarkers by more than 75% and improved patients' QoL, whereas ozonated blood via minor autohemotherapy improved significantly (p < 0.001) WOMAC and Lequesne's parameters in knee osteoarthritis. CONCLUSIONS: The models described, i.e., ozone autohemotherapy in wound antimicrobial treatment and ozonated blood in knee osteoarthrosis, following our protocols, share the outstanding ability of ozone to modulate the innate immune response and address bacterial clearance as well as inflammation and pain.

Cytokine profiles in COVID-19 patients undergoing adjunct ozone therapy: some comments.

A comment to: Ghaleh HEG, Izadi M, Javanbakht M, Ghanei M, Einollahi B, Jafari NJ, Alishiri G, Aslani J, Abolghasemi H, Simonetti V, Khafaei M, Zhao S, Saadat SH, Ahmadi M, Parvin S, Vazifedoust S, Alvanagh AG. Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement. Inflammopharmacology. 2023 Jul 12. https://doi.org/10.1007/s10787 -023-01288-9.

Medicinal Plant-Derived Phytochemicals in Detoxification.

The average worldwide human life expectancy is 70 years, with a significantly higher value in Western societies. Many modern diseases are not associated with premature mortality but with a decreased quality of life in aged patients and an excessive accumulation of various toxic compounds in the human body during life. Today, scientists are especially interested in finding compounds that can help increase a healthy lifespan by detoxifying the body. Phytotherapy with specific approaches is used in alternative medicine to remove toxins from the body. Worldwide, research is conducted to identify medicinal plant-derived molecules that, with few or no side effects, may protect the liver and other organs. This review provides updated information about the detoxification process, the traditional and modern use of the most effective medicinal plants, their active metabolites as detoxifying agents, and the mechanisms and pathways involved in the detoxification process. Among medicinal plants with substantial detoxifying properties, a major part belongs to the Asteraceae family (Silybum marianum, Cynara scolymus, Arctium lappa, Helichrysum spp, Inula helenium, and Taraxacum officinale). The most widely used hepatoprotective phytocomponent is silymarin, a standardized extract from the Silybum marianum seeds containing a mixture of flavonolignans. Many polysaccharides, polyphenols, and terpenoids have a detoxifying effect. Overall, scientific data on medicinal plants used in phytotherapeutic practice worldwide provides an understanding and awareness of their efficacy in detoxification.

Natural Compounds and Products from an Anti-Aging Perspective.

Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro- and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants' fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water.

Combined Supplementation of Coenzyme Q10 and Other Nutrients in Specific Medical Conditions.

Coenzyme Q10 (CoQ10) is a compound with a crucial role in mitochondrial bioenergetics and membrane antioxidant protection. Despite the ubiquitous endogenous biosynthesis, specific medical conditions are associated with low circulating CoQ10 levels. However, previous studies of oral CoQ10 supplementation yielded inconsistent outcomes. In this article, we reviewed previous CoQ10 trials, either single or in combination with other nutrients, and stratified the study participants according to their metabolic statuses and medical conditions. The CoQ10 supplementation trials in elders reported many favorable outcomes. However, the single intervention was less promising when the host metabolic statuses were worsening with the likelihood of multiple nutrient insufficiencies, as in patients with an established diagnosis of metabolic or immune-related disorders. On the contrary, the mixed CoQ10 supplementation with other interacting nutrients created more promising impacts in hosts with compromised nutrient reserves. Furthermore, the results of either single or combined intervention will be less promising in far-advanced conditions with established damage, such as neurodegenerative disorders or cancers. With the limited high-level evidence studies on each host metabolic category, we could only conclude that the considerations of whether to take supplementation varied by the individuals' metabolic status and their nutrient reserves. Further studies are warranted.

Natural Dietary Compounds in the Treatment of Arsenic Toxicity.

Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.

Neurotransmitters Regulation and Food Intake: The Role of Dietary Sources in Neurotransmission.

Neurotransmitters (NTs) are biologically active chemicals, which mediate the electrochemical transmission between neurons. NTs control numerous organic functions particularly crucial for life, including movement, emotional responses, and the physical ability to feel pleasure and pain. These molecules are synthesized from simple, very common precursors. Many types of NTs have both excitatory and inhibitory effects. Neurotransmitters' imbalance can cause many diseases and disorders, such as Parkinson's disease, depression, insomnia, increased anxiety, memory loss, etc. Natural food sources containing NTs and/or their precursors would be a potential option to help maintain the balance of NTs to prevent brain and psychiatric disorders. The level of NTs could be influenced, therefore, by targeting dietary habits and nutritional regimens. The progressive implementation of nutritional approaches in clinical practice has made it necessary to infer more about some of the nutritional NTs in neuropsychiatry. However, the importance of the intake of nutritional NTs requires further understanding, since there are no prior significant studies about their bioavailability, clinical significance, and effects on nerve cells. Interventional strategies supported by evidence should be encouraged.

The role of B vitamins in stroke prevention.

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B12 deficiency is a nutritional determinant of total Hcy and stroke risk. Genetic factors may link B vitamins with stroke severity due to the impact on Hcy metabolism of polymorphism in the genes coding for methylenetetrahydrofolate reductase, methionine-synthase, methionine synthase reductase, and cystathionine ß-synthase. Several meta-analyses of large randomized controlled trials exist. However, they are not completely in agreement about B vitamins' role, particularly folic acid levels, vitamin B12, and B6, in lowering the homocysteine concentrations in people at high stroke risk. A very complex relationship exists between Hcy and B vitamins, and several factors appear to modify the preventive effects of B vitamins in stroke. This review highlights the regulating factors of the active role of B vitamins active in stroke prevention. Also, inputs for further large, well-designed studies, for specific, particularly sensitive subgroups are given.

The Role of Diet and Supplementation of Natural Products in COVID-19 Prevention.

Recently, a discussion has begun on the global management strategy against COVID-19 based on the hypothesis that individuals' macro- and micronutrient status combined with antiviral drugs and herbs can be an ally against the infection. The hypothesis is that people's nutritional and oxidative scavenging capacity may provide fundamental data to predict severe and acute pulmonary distress following SARS-Cov2 infection. Consequently, the scientific community has addressed the role of balanced diets, nutritional supplements, and micronutrients, including folk herbal formulations, in reducing hospitalization and the severity of pulmonary impact in COVID-19 by preventing the most serious forms of the infection. This led to an animated debate on the potential effectiveness of some vitamins, micronutrients, and traditional Chinese medicine in preventing COVID-19, with some authors convinced that plant extracts could act oppositely, exacerbating the effect of the infection. While current research is still far to assess the suggestions and issues raised in this short communication, it is undoubtedly true that determining an individual's current metabolic status, including macro- and micronutrients, is an essential factor in defining any individuals' deficiencies, which will need to be addressed urgently through a proper diet, specific personalized nutritional supplementation, and lifestyle changes.

Iron Deficiency in Obesity and after Bariatric Surgery.

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass-RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects' iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.

Insights into the Effects of Dietary Omega-6/Omega-3 Polyunsaturated Fatty Acid (PUFA) Ratio on Oxidative Metabolic Pathways of Oncological Bone Disease and Global Health.

Various nutrients have been designated as antioxidants, with a possible effect on diseases like cancer. This is partly due to their effect on prostaglandins, thereby affecting local pathological metabolic acidosis. This paper aims to summarize the culprit pathophysiological mechanisms involved, with a focus on the bone microenvironment. The omega- 6/omega-3 PUFA ratio is particularly investigated for its antioxidative effects, countering these pathways to fight the disease. This feature is looked at concerning its impact on health in general, with a particular focus on malignant bone metastasis.

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Greatly Improved Fatigue Symptoms When Treated with Oxygen-Ozone Autohemotherapy.

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic syndrome characterized by fatigue as its major and most outstanding symptom. Previous evidence has supported the ability of ozone to relief ME/CFS related fatigue in affected patients (2) Methods: A number of 200 ME/CFS previously diagnosed patients, (mean age 33 ± 13 SD years) were consecutively treated with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was evaluated via an FSS 7-scoring questionnaire before and following 30 days after treatment. (3) Results: Almost half (43.5%) of the treated patients evolved their FSS scale from the worst (7) to the best (1) score, assessing the highest improvement from being treated with O2-O3-AHT. Furthermore 77.5% of patients experienced significant ameliorations of fatigue, of 4-6 delta score. No patient showed side effects, yet experienced long lasting fatigue disappearance, by three months follow up (4) Conclusions: Treatment with O2-O3-AHT greatly improves ME/CFS related fatigue, aside from sex and age distribution.

Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O2-O3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a syndrome that has fatigue as its major symptom. Evidence suggests that ozone is able to relieve ME/CFS-related fatigue in affected patients. (2) Objective: To evaluate whether differences exist between males and females in ozone therapy outputs in ME/CFS. (3) Methods: In total, 200 patients previously diagnosed with ME/CFS (mean age 33 ± 13 SD years) underwent treatment with oxygen-ozone autohemotherapy (O2-O3-AHT). Fatigue was investigated via an FSS 7-scoring questionnaire before and following 1 month after treatment. (4) Results: The Mann-Whitney test (MW test) assessed the significance of this difference (H = 13.8041, p = 0.0002), and female patients showed better outcomes than males. This difference was particularly striking in the youngest age cohort (14-29 years), and a KW test resulted in H = 7.1609, p = 0.007 for the Δ = 28.3% (males = 3.8, females = 5.3). (5) Conclusions: When treated with O2-O3-AHT, females respond better than males.

Oxygen-ozone (O2-O3) immunoceutical therapy for patients with COVID-19. Preliminary evidence reported.

OBJECTIVE: This study evaluated the potential efficacy of a novel approach to treat COVID-19 patients, using an oxygen-ozone (O2-O3) mixture, via a process called Oxygen-Ozone- Immunoceutical Therapy. The methodology met the criteria of a novel, promising approach to treat successfully elderly COVID-19 patients, particularly when hospitalized in intensive care units (ICUs) Experimental design: We investigated the therapeutic effect of 4 cycles of O2-O3 in 50 hospitalized COVID-19 subjects suffering from acute respiratory disease syndrome (ARDS), aged more than 60 years, all males and undergoing non invasive mechanical ventilation in ICUs. RESULTS: Following O2-O3 treatment a significant improvement in inflammation and oxygenation indexes occurred rapidly and within the first 9 days after the treatment, despite the expected 14-20 days. A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer) was observed. Furthermore, amelioration in the major respiratory indexes, such as respiratory and gas exchange markers (SatO2%, PaO2/FiO2 ratio), was reported. CONCLUSION: Our results show that O2-O3 treatment would be a promising therapy for COVID-19 patients. It leads patients to a fast recovery from ARDS via the improvement of major respiratory indexes and blood gas parameters, following a relatively short time of dispensed forced ventilation (about one to two weeks). This study may encourage the scientific community to further investigate and evaluate the proposed method for the treatment of COVID-19 patients.