Fermented Carica papaya and Morinda citrifolia as Perspective Food Supplements for the Treatment of Post-COVID Symptoms: Randomized Placebo-Controlled Clinical Laboratory Study.

Food supplements based on fermented Carica papaya and Morinda citrifolia, known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms.

Anti-Bacterial and Anti-Inflammatory Effects of Toothpaste with Swiss Medicinal Herbs towards Patients Suffering from Gingivitis and Initial Stage of Periodontitis: from Clinical Efficacy to Mechanisms.

OBJECTIVE: To distinguish clinical effects and mechanisms of sodium monofluorophosphate plus xylitol and herbal extracts of Swiss medicinal plants (Chamomilla recutita, Arnica montana, Echinacea purpurea, and Salvia officinalis). MATERIALS AND METHODS: A 2-month-long comparative clinical study of toothpaste containing 1450 ppm sodium monofluorophosphate and xylitol (control, 15 patients) and toothpaste additionally containing extracts of the medicinal herbs (experiment, 35 patients) was performed on patients with gingivitis and the initial stage of periodontitis. Clinical indices of gingivitis/periodontitis were quantified by Loe & Silness's, CPITN, OHI-S, and PMA indexes. The pro-inflammatory and anti-inflammatory interleukins, nitrites/nitrates, total antioxidant activity, and bacterial pattern characteristic for gingivitis and periodontitis were quantified in the gingival crevicular fluid and plaque. In the in vitro tests, direct anti-bacterial effects, inhibition of catalase induction in Staphylococcus aureus, in response to oxidative burst of phagocytes, and intracellular bacterial killing were determined for the toothpastes, individual plant extracts, and their mixture. RESULTS: Experimental toothpaste was more efficient clinically and in the diminishing of bacterial load specific for gingivitis/periodontitis. Although the control toothpaste exerted a direct moderate anti-bacterial effect, herbal extracts provided anti-inflammatory, anti-oxidant, direct, and indirect anti-bacterial actions through inhibition of bacterial defence against phagocytes. CONCLUSIONS: Chemical and plant-derived anti-bacterials to treat gingivitis and periodontitis at the initial stage should be used in combination amid their different mechanisms of action. Plant-derived actives for oral care could substitute toxic chemicals due to multiple modes of positive effects.

Is there a role for antioxidants in the prevention of infection-associated carcinogenesis and in the treatment of infection-driven tumors?

Causative connections between infections and cancer are ascertained for several types of viruses, bacteria, and parasites. The mechanisms of cancer induction in chronically infected inflamed tissues strongly implicate oxygen- and nitrogen-centered reactive species, and an impairment of redox-sensitive molecular pathways involved in the tumorigenic transformation, tumor growth, altered immune defense, and in the mechanisms of tumor cell death and survival. Here, we briefly reviewed mechanistic data on carcinogenesis and tumor progression of three major infection-associated tumors, human papillomavirus-induced cervical cancer, hepatitis B virus-positive hepatocarcinoma, and Helicobacter pylori-positive gastric cancer. Notwithstanding the contradictory results of clinical studies on cancer chemoprevention with long-term, high dosage antioxidant vitamin/micronutrient supplementation, natural and synthetic agents with proven capacity to affect redox-dependent molecular pathways still hold the promise for preventing/delaying carcinogenesis initiation, as well as the overt malignancy evolution from dysplastic/ aplastic stages. Novel directions for a targeted antioxidant-based approach to the reduction of persistent infection-driven cancer risk stems from the current knowledge of critical factors in the host-microbe interaction leading to oncogenesis. An emerging role of redox active substances in the chemotherapy of tumors relies on their stimulating effects towards TRAIL-related apoptosis and the induction of intracellular oxidative stress.

Is there a Role For Antioxidants in the Prevention of Infection-Associated Carcinogenesis and in the Treatment of Infection-Driven Tumors?

Causative connections between infections and cancer are ascertained for several types of viruses, bacteria, and parasites. The mechanisms of cancer induction in chronically infected inflamed tissues strongly implicate oxygen- and nitrogen-centered reactive species, and an impairment of redox-sensitive molecular pathways involved in the tumorigenic transformation, tumor growth, altered immune defense, and in the mechanisms of tumor cell death and survival. Here, we briefly reviewed mechanistic data on carcinogenesis and tumor progression of three major infection-associated tumors, human papillomavirus-induced cervical cancer, hepatitis B virus-positive hepatocarcinoma, and Helicobacter pylori-positive gastric cancer. Notwithstanding the contradictory results of clinical studies on cancer chemoprevention with long-term, high dosage antioxidant vitamin/micronutrient supplementation, natural and synthetic agents with proven capacity to affect redox-dependent molecular pathways still hold the promise for preventing/delaying carcinogenesis initiation, as well as the overt malignancy evolution from dysplastic/aplastic stages. Novel directions for a targeted antioxidant-based approach to the reduction of persistent infection-driven cancer risk stems from the current knowledge of critical factors in the host-microbe interaction leading to oncogenesis. An emerging role of redox active substances in the chemotherapy of tumors relies on their stimulating effects towards TRAIL-related apoptosis and the induction of intracellular oxidative stress.

Coenzyme Q(10), vitamin E, selenium, and methionine in the treatment of chronic recurrent viral mucocutaneous infections.

OBJECTIVE: Host defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections. METHODS: Two controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q(10), RRR-α-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNα/γ) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions. RESULTS: In both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups. CONCLUSIONS: Results document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections.

Clinical and biochemical effects of coenzyme Q(10), vitamin E, and selenium supplementation to psoriasis patients.

OBJECTIVE: The aim of the present study was to evaluate clinical effects of supplementation with antioxidants to patients with severe erythrodermic (EP) and arthropathic (PsA) forms of psoriasis. METHODS: Fifty-eight patients were hospitalized, treated by conventional protocols, and randomly assigned to four groups. Groups EP1 and PsA1 were supplemented with coenzyme Q(10) (ubiquinone acetate, 50 mg/d), vitamin E (natural alpha-tocopherol, 50 mg/d), and selenium (aspartate salt, 48 mug/d) dissolved in soy lecithin for 30-35 d. Groups EP2 and PsA2 (placebo) received soy lecithin. Clinical conditions were assessed by severity parameters. Markers of oxidative stress included superoxide production, copper/zinc-superoxide dismutase, and catalase activities in the circulating granulocytes, in the affected epidermis, and plasma levels of nitrites/nitrates. RESULTS: At baseline patients had an increased superoxide release from granulocytes (10.0 +/- 0.5, 2.9 +/- 0.2, and 1.5 +/- 0.1 nmol/L per 10(6) cells/h for EP, PsA, and donors, respectively), increased copper/zinc-superoxide dismutase and catalase activities in granulocytes in EP patients and decreased in PsA patients, decreased activity of copper/zinc-superoxide dismutase (0.3 +/- 0.0, 1.8 +/- 0.1, and 2.2 +/- 0.2 U/mg protein for EP, PsA, and donors, respectively), and altered activity of catalase in psoriatic epidermis. Plasma levels of nitrites/nitrates were greater than normal in psoriatic patients. Supplementation resulted in significant improvement of clinical conditions, which corresponded to the faster versus placebo normalization of the oxidative stress markers. CONCLUSION: Supplementation with antioxidants coenzyme Q(10), vitamin E, and selenium could be feasible for the management of patients with severe forms of psoriasis.