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

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

Histamine Intolerance—The More We Know the Less We Know. A Review

The intake of food may be an initiator of adverse reactions. Food intolerance is an abnormal non-immunological response of the organism to the ingestion of food or its components in a dosage normally tolerated. Despite the fact that food intolerance is spread throughout the world, its diagnosing is still difficult. Histamine intolerance (HIT) is the term for that type of food intolerance which includes a set of undesirable reactions as a result of accumulated or ingested histamine. Manifestations may be caused by various pathophysiological mechanisms or a combination of them. The problem with a “diagnosis” of HIT is precisely the inconstancy and variety of the manifestations in the same individual following similar stimuli. The diagnosing of HIT therefore requires a complex time-demanding multidisciplinary approach, including the systematic elimination of disorders with a similar manifestation of symptoms. Among therapeutic approaches, the gold standard is a low-histamine diet. A good response to such a diet is considered to be confirmation of HIT. Alongside the dietary measures, DAO supplementation supporting the degradation of ingested histamine may be considered as subsidiary treatment for individuals with intestinal DAO deficiency. If antihistamines are indicated, the treatment should be conscious and time-limited, while 2nd or 3rd generation of H1 antihistamines should take precedence.</jats:p

Histamine Intolerance—The More We Know the Less We Know. A Review

The intake of food may be an initiator of adverse reactions. Food intolerance is an abnormal non-immunological response of the organism to the ingestion of food or its components in a dosage normally tolerated. Despite the fact that food intolerance is spread throughout the world, its diagnosing is still difficult. Histamine intolerance (HIT) is the term for that type of food intolerance which includes a set of undesirable reactions as a result of accumulated or ingested histamine. Manifestations may be caused by various pathophysiological mechanisms or a combination of them. The problem with a “diagnosis” of HIT is precisely the inconstancy and variety of the manifestations in the same individual following similar stimuli. The diagnosing of HIT therefore requires a complex time-demanding multidisciplinary approach, including the systematic elimination of disorders with a similar manifestation of symptoms. Among therapeutic approaches, the gold standard is a low-histamine diet. A good response to such a diet is considered to be confirmation of HIT. Alongside the dietary measures, DAO supplementation supporting the degradation of ingested histamine may be considered as subsidiary treatment for individuals with intestinal DAO deficiency. If antihistamines are indicated, the treatment should be conscious and time-limited, while 2nd or 3rd generation of H1 antihistamines should take precedence

Beneficial effects of pleuran on asthma control and respiratory tract-infection frequency in children with perennial asthma

Abstract The aim of this study was to evaluate the effects of pleuran (β-glucan isolated from Pleurotus ostreatus) on asthma control and respiratory morbidity in children on conventional GINA-based asthma treatment who had partially controlled perennial asthma. A double-blind, placebo-controlled multicentre clinical trial with a 2-arm, parallel design was conducted across three countries; 230 children aged 7 to 17 years were randomised (1:1) into an active group (receiving a pleuran/vitamin C combination) or a placebo group (receiving vitamin C only). This study consisted of 24 weeks of treatment (2 capsules a day) and then 24 weeks of follow-up. The primary endpoints included the effects of active treatment versus placebo on asthma control and respiratory tract infections (RTIs). Secondary endpoints included changes in the following measures: number of asthma exacerbations, with or without respiratory infection; quality of life of both asthmatic children and their caregivers; spirometric indices; fractional exhaled nitric oxide (FeNO) levels; safety after 24 weeks of treatment and also after the full 48-week study period. Overall, 206 children completed this study; 113 of these children were in the active group and received a pleuran/vitamin C combination for 24 weeks. After the 24-week treatment period, children below 12 years of age who were in the active group achieved significant improvements in asthma control compared to those in the placebo group (21.8 ± 3.5 vs. 20.3 ± 4.0; P = 0.02); while children at least 12 years old who were in the active group reported lower numbers of RTIs (0.7 ± 1.0 vs. 1.9 ± 1.7; P = 0.002) compared to children of this age in the placebo group. In addition, children below 12 years of age in the active group showed a significant decrease in asthma exacerbations compared to those in the placebo group (2.5 ± 1.6 vs. 3.3 ± 1.9; P = 0.05). At the end of the 48-week trial, a statistically significant improvement in asthma control was observed in 84.7% of children who received pleuran/vitamin C treatment compared to 67.0% of children who received vitamin C only (P = 0.01). The pleuran/vitamin C combined treatment was safe and well-tolerated, and no related serious adverse events were reported. This study highlights the favourable safety profile of pleuran/vitamin C supplementation and demonstrates positive effects of this treatment on asthma control and RTI incidence in children with allergic perennial asthma that was partially controlled by conventional therapy