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.