An update on nutritional factors and COVID-19, 27th September 2020

This week I review recent studies on COVID-19 and nutritional therapies. These are hypothesis generating but do support the role of a healthy diet during the pandemic and beyond.

On March 14th, just prior to the first lockdown in the UK, I wrote an article summarising the dietary and lifestyle factors that are important in maintaining a healthy immune system. I highlighted the role of certain nutrients, including flavonoids, vitamin C, selenium and zinc. I discussed the importance of adequate vitamin D intake and maintaining a healthy gut microbiome. I concluded that a diet focussed on whole plant foods and minimising animal-derived and processed foods is associated with better health and a more robust immune system.

Since then, a number of papers and review articles have been published on the topic in relation to SARS-CoV-2 infection and the disease it causes, COVID-19. Some papers are still in pre-print and and I consider most as hypothesis generating. Nonetheless, the data are remarkably consistent with prior knowledge and support a diet pattern centred around whole plant foods.

Importantly, we now better understand the risk factors that predict for a worse outcome with SARS-Co-V-2 infection. Some of these risk factors of course can not be changed such as advanced age, male sex and socioeconomic status. However, the risk factors that we might be able to impact through a diet and lifestyle approach are overweight and obesity, hypertension, cardiovascular disease and type 2 diabetes. Some, but not all, of the increased risk faced by communities of colour are related to a higher incidence of underlying health conditions.

Do not misinterpret what I am saying here. SARS-Co-V-2 is an infectious disease and the only way to prevent infection currently is through physical distancing and impeccable hygiene measures. Nonetheless, this virus is not going to disappear. We have to remember that the 1918 pandemic lasted for 2 years. We are all hoping for a safe and effective vaccine, but until that time, our best option is to keep in the best of health and take on learning from the ‘first wave’. With this in mind, the UK Government have launched their obesity strategy, which aims to support people to lose weight.

So what has the scientific literature taught us so far?

Nutritional factors that impact entry of SARS-Co-V-2 into cells: Viruses need to gain entry into cells to wreak havoc. SARS-CoV-2 enters using the ACE2 receptor found on a variety of cells, including those of the lung lining. Blocking binding to the receptor and hence entry into cells is one approach to reducing the severity of the infection. A recent laboratory study has shown that cholesterol plays an important role in viral entry. When cells have a high amount of cholesterol in them, which happens with aging, obesity and type 2 diabetes, there is enhanced entry and infectivity of the virus. It’s not the blood cholesterol level that’s important but the cholesterol in the cells. However, in people with high blood cholesterol, overtime, this will accumulate in various cells, including those in the lung and immune cells, such as macrophages. The authors hypothesise that drugs, such as statins, that inhibit cholesterol synthesis may play a role. Thus is could also be hypothesised that diets associated with lower blood cholesterol levels, such as a whole food plant-based diet, may also be of help.

Another interesting laboratory paper has shown that specific molecules extracted from edible seaweeds called sulfated polysaccharides can prevent the binding of SARS-CoV-2 to cells by acting as a decoy and binding the virus instead. These molecules appear to be more potent than the licensed drug remdesivir. The authors suggest that these compounds could be effective as a nasal spray to prevent infection.

Inhibiting viral replication: Many pharmaceutical drugs for SARS-CoV-2 have focused on inhibiting the main protease, a key protein in the virus’ lifecycle, which allows it to replicate. A number of nutritional compounds have been investigated for their anti-viral properties and ability to inhibit the viral protease in the laboratory. No surprise, the compounds that come out top are the polyphenol compounds found in plants, especially flavonoids and the polyphenol compounds in green tea. Quercetin, a flavonoid I discussed back in March, continues to be of interest to researchers, with one US institution including it in their treatment algorithms.

Reducing the severity of infection: Once infected with the pandemic virus, can the severity be reduced? Researchers are asking just this question. What is emerging is that the health of the gut microbiome may predict the severity of COVID-19. One study showed that Lactobacillus and Ruminococcus species for example were associated with higher levels of interferon-gamma, an anti-viral cytokine, and better outcomes from COVID-19. These microbiome effects were negatively impacted by various underlying health conditions, such as high blood pressure, blood glucose, blood lipids and medicine use for type 2 diabetes. Green and black tea, polyunsaturated fatty acids and fibre were correlated with improved gut microbiome signatures. We know that the bacteria in our gut have an important role to play in maintaining a healthy immune system and if we don’t feed our gut bacteria appropriately, our immune system will suffer. Studies examining food consumption have suggested certain foods such as cabbage and fermented vegetables, known to promote the growth of healthy gut bacteria, may reduce the risk of death from COVID-19. There is prior evidence to support the theory that gut bacteria may improve outcomes from infections, with probiotics reducing the severity of respiratory infections in children and adults and reduced risk of pneumonia in patients on mechanical ventilation. There is also cross talk between the gut and lung microbiota, with both being important for local and systemic immunity.

COVID-19 is a vascular disease: We now know that SARS-Co-V2 affects the cells lining the blood vessels, the endothelial cells, by directly invading them and causing endothelitisinflammation of the blood vessels. This is not only seen in the lung but occurs outside the lung too. One example is of this is the loss of smell where the virus infects the vascular cells of the olfactory system because the ACE2 receptor that the virus latches onto is found on vascular cells and pericytes within the olfactory system. Another example is the recognition of ‘COVID toe” which is a consequence of inflammation of the blood vessels in the skin. In the context of cardiovascular disease, we know that dietary factors impact endothelial function and clinical outcomes. The Western diet pattern high in saturated fat, salt and sugar adversely affects the health of endothelial cells, whereas diets centred around whole plant foods, with an emphasis on unsaturated fatty acids, vitamins, antioxidants and foods that generate nitric oxide, such as leafy greens, improve endothelial function and cardiovascular outcomes. It is of course a leap to suggest diet could impact the effect of SARS-Co-V 2 on endothelial cells, but we already know that patients who have underlying cardiovascular diseases have a worse outcomes, suggesting that improving endothelial function may be of benefit.

COVID-19 induces an extreme inflammatory response- cytokine storm. This is caused by immune dysregulation and is at the core of the severe reactions experienced by those infected with SARS-Co-V-2. Individuals who are already suffering with underlying inflammatory conditions and a defective immune system, including overweight/obesity, type 2 diabetes, cardiovascular disease and cancers, are at higher risk of this extreme inflammatory reaction. Long-term consequences are a real concern. Even after symptomatic recovery from COVID-19, regardless of whether the infection was mild or severe, there is evidence of ongoing damage to vital organs. For example, this study performed cardiac MRI scans on 100 patients who had recovered from COVID-19 and found that 60% of people had evidence of ongoing inflammation affecting the heart. Many have hypothesised that reducing inflammation and promoting a healthier immune system through a diet and lifestyle approach may help reduce the severity of the inflammatory response. An interesting study in a laboratory model of COVID-19 lung injury showed that beta-glucans from mushrooms can reduce the inflammatory response, reducing the levels of certain cytokines involved in the cytokine storm. I wrote about beta-glucans back in March in relation to the form of beta-glucan found in nutritional yeast. Beta-glucans are a group of polysaccharides found in the cell wall of yeast and fungi and have been shown to positively impact the functioning of the immune function.

Avoiding nutritional deficiencies: Micronutrient deficiencies are not uncommon in those on a standard Western diet, which in the UK consists predominantly of ultra-processed foods and is severely deficient in fruits and vegetables. Although the data are not clear cut there is evidence that inadequate levels of selenium and zinc may adversely affect outcomes and ensuring adequate intake should be a priority. In addition, there has been much debate on the role of vitamin D in predicting outcomes from COVID-19. Although often categorised as a nutrient, vitamin D is really a hormone and best obtained by regularly exposing the skin to sunlight. However, for many in the current situation, this is not possible and therefore we rely on supplemented food sources and supplements. Some, but not all, studies suggest that inadequate levels of vitamin D are implicated in the severity of COVID-19. Given the importance of vitamin D in the functioning of the immune system, it is strongly advised that adequate levels are achieved and for most this will require a supplement. Dosage of vitamin D is a matter of debate with many advocating for higher doses, 1000–2000IU per day, compared to the 400IU recommended by the UK Government.

Whether supranutritional doses of vitamins and micronutrients are of value in severe COVID-19 infection is an open question, but there are suggestions in the scientific literature that high doses of antioxidants such as vitamin C may benefit critically ill patients.

Future studies: The information I have summarised is being taken forward into clinical trials for patients with SARS-CoV-2. A randomised double-blind, placebo-controlled trial from the UK is evaluating the influence of a phytochemical-rich nutritional intervention and a lactobacillus (probiotic) supplement on clinical outcomes among individuals with COVID-19 infection and their co-inhabitants. A Chinese study is investigating high doses of vitamin C for those with severe COVID-19. Several studies are investigating the role of probiotics to reduce the severity of infection and to reduce the risk of infection in household contacts. Vitamin D supplementation is also being investigated as a means of reducing disease severity.

Conclusions: The information discussed in this article is hypothesis generating. However, the evidence points to using diet and nutrition to maintain good health during the pandemic and beyond. A healthy plant-based diet, low in cholesterol and saturated fat, yet high in beneficial phytonutrients, is associated with some of the lowest risks of overweight and obesity and other common chronic diseases, including cardiovascular disease, type 2 diabetes and certain cancers. A plant-based diet improves endothelial function and reduces inflammation. Although we can’t yet recommend using probiotic supplements for COVID-19, we can improve the health of the gut microbiome by eating a fibre-rich diet and including some fermented plant foods with beneficial changes possible within days to weeks.

Broader conclusions and learning: It must not be forgotten that our diet choices will determine the risk of future pandemics. Most new and emerging infections are caused by the use of animals as food and the destruction of their natural habitats. The biggest contributor to habitat destruction and species loss is animal apiculture. If we continue consuming meat and dairy, most of which is produced in factory farms, more pandemic infections are inevitable. In the words of the scientists that have sounds the alarm and warned that we are accelerating towards the sixth mass extinction event, ‘There is time, but the window of opportunity is almost closed. We must save what we can, or lose the opportunity to do so forever. There is no doubt, for example, that there will be more pandemics if we continue destroying habitats and trading wildlife for human consumption as food and traditional medicines. It is something that humanity cannot permit, as it may be a tipping point for the collapse of civilization. What is at stake is the fate of humanity and most living species. Future generations deserve better from us’.

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