Conclusion
Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, also potent Nrf2 activators. 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.
Mainstream COVID-19 control strategies including social distancing, confinement and intensive case finding, testing, tracing and isolating are so far not enough to provide a SARS-CoV-2-free environment and restore a safe social life. There are hopes for a safe and effective vaccine, but this is unlikely to become rapidly available. So, there is a need to explore other potentially useful strategies. An area that has not been sufficiently considered is diet, both as a preventive and/or therapeutically useful intervention, encouraging people to eat more traditional foods containing fermented vegetables. We have suggested that fermented vegetables could be associated with a lower COVID-19 mortality due to their potent antioxidant effect among which sulforaphane and LAB are important. However, many other foods may have a similar activity. It should be noted that dietary supplements that over-activate Nrf2 may have side-effects.136
Robust evidence from observational studies would be helpful to formally investigate associations between fermented foods and clinical outcomes in COVID-19. State-of-the-art methods, including the use of DAGs (Directed Acyclic Graphs), may be needed to help assess whether the associations seen are likely to represent causal relationship137. A faster approach would be to develop large clinical trials in the appropriate populations. Interventions based on diets with a high intake of fermented foods like Kimchi or other fermented foods are unlikely to present ethical difficulties. Furthermore, the fact that a precise mechanism has been proposed would facilitate adding reliable biomarkers to the relevant clinical outcomes. Moreover, new drugs based on the components of these fermented foods may be of interest.
If the hypothesis is proved, COVID-19 will be the first infectious disease outbreak associated with a loss of “nature”138 and to be ascribed as a disease of the Anthropocene 139. Imbalance in the gut microbiota is responsible for the pathogenesis of various disease types including allergy, asthma, rheumatoid arthritis, different types of cancer, diabetes mellitus, obesity and cardiovascular disease140. Fermentation was introduced during the Neolithic age and was essential for the survival of human kind. When modern life led to eating reduced amounts of fermented foods, the microbiome drastically changed 141, allowing SARS-CoV-2 to spread or to be more severe 142. It is time for mitigation143.