Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Υπεροξείδιο του υδρογόνου στο συμπύκνωμα του εκπνεόμενου αέρα ασθενών με φλεγμονώδεις παθήσεις των αεραγωγών

Hydrogen peroxide in expired breath condensate of patients with inflammatory airway diseases. Stelios Loukides MD, Pneumonology Dept Athens Army General Hospital. The aim of our study was to determine the concentration of exhaled hydrogen peroxide (H2O2) in patients with inflammatory airway diseases, to investigate which cells are the main source of hydrogen peroxide (H2O2) production in each disease and finally to evaluate the association between H2O2 levels, airway inflammation and disease severity. Thirty patients with bronchiectasis, fifty stable asthmatics with disease severity ranging from mild to moderate and finally thirty patients with stable COPD with disease severity ranging from mild to severe were studied. Mean concentration of H2O2 was significantly elevated in patients with inflammatory airway diseases compared to the values of control subjects for each disease. Eosinophils were the predominate cells which generate H2O2 in asthma, while neutrophils were responsible for the highest levels which were observed in bronchiectasis and COPD. The role of H2O2 concentration in predicting the severity of the disease as well as the inflammatory process, is limited in asthma and depends on the use of inhaled steroids (ICS) and the classification severity. In patients with bronchiectasis increased levels of exhaled H2O2 reflected the severity of the disease as well as the inflammatory process, were not decreased either by the use of ICS or the long term oral antibiotic treatment but were significantly affected by chronic colonization with Pseudomonas Aeruginosa. In patients with COPD the role of H2O2 concentration in predicting the severity of the disease as well as the inflammatory process depends on the classification severity and was not affected by the use of inhaled steroids.Σκοπός της μελέτης αυτής ήταν η μέτρηση των επιπέδων του υπεροξειδίου του υδρογόνου (H2O2) στο συμπύκνωμα του εκπνεόμενου αέρα ασθενών με φλεγμονώδεις παθήσεις των αεραγωγών, ο καθορισμός των κυττάρων που συμμετέχουν στην παραγωγή του για κάθε νόσο ξεχωριστά, καθώς και η πιθανή συσχέτιση των επιπέδων του με παραμέτρους που εκφράζουν φλεγμονή και βαρύτητα σε κάθε νόσο. Μελετήθηκαν τριάντα ασθενείς με βρογχεκτασίες, πενήντα ασθενείς με σταθερό άσθμα βαρύτητας από ήπιο έως μέτριο και τριάντα ασθενείς με σταθερή ΧΑΠ βαρύτητας από ήπια έως σοβαρή. Η μέση συγκέντρωση του H2O2 ήταν στατιστικά σημαντικά υψηλότερη από αυτή των ομάδων ελέγχου για κάθε νόσο. Τα ηωσινόφιλα ήταν τα επικρατούντα κύτταρα που συμμετείχαν στην παραγωγή H2O2 στο άσθμα, ενώ τα ουδετερόφιλα ήταν υπεύθυνα για την υψηλή συγκέντρωση του H2O2 στις βρογχεκτασίες και στην ΧΑΠ. Ο ρόλος του H2O2 στην αξιολόγηση της υποκείμενης φλεγμονής και βαρύτητας στο άσθμα ήταν περιορισμένος μια και εξαρτώνταν από την λήψη εισπνεομένων στεροειδών (ΕΣ) και την ταξινόμηση αυτής σε στάδια. Στους ασθενείς με βρογχεκτασίες τα επίπεδα του H2O2 εξέφραζαν την υποκείμενη φλεγμονή της νόσου, την έκταση και την βαρύτητα αυτής, μη επηρεαζόμενα από την λήψη ΕΣ και αντιβιοτικών σε μακρό χρόνο, αλλά σημαντικά επηρεαζόμενα από τον χρόνιο αποικισμό με Ψευδομονάδα Aeruginosa. Τέλος στους ασθενείς με ΧΑΠ ο ρόλος του H2O2 στην αξιολόγηση της υποκείμενης φλεγμονής και βαρύτητας επηρεαζόταν από την ταξινόμηση αυτής σε στάδια αλά όχι από την λήψη ΕΣ