During these worrying and challenging times, we are getting a lot of queries about how best to support resilience to infections. As COVID-19 is caused by a novel virus there is limited research with regards to specific support that may be useful. However, evidence is available for interventions which support immunity, protect against viral infections and may possess antiviral activity. In addition, new research is emerging all the time with regards to interventions that have the potential to be useful against this specific strain, as well as other strains of coronavirus.

Key Takeaways

• • COVID-19 is caused by a strain of corona virus known as SARS-CoV2. This enters the body via ACE2 receptors and utilises enzymes including SARS-CoV 3C-like protease (3CLpro) to replicate. Individuals who have had severe symptoms of COVID-19 have experienced a cytokine storm where inflammatory molecules have run away with inflammation.
  • Interventions for supporting immune function, inhibiting viral replication and modulating inflammation may all be useful in supporting protection against severity of infection.
  • Nutrients with immune supporting functions include vitamin c, vitamin D, vitamin zinc, selenium and beta glucans.
  • Zinc, iron and manganese are all co-factors for enzymes and have been implicated in inhibiting viral replication.
  • Research suggests SARS-Cov-2 virus enters cells via ACE2 by binding to zinc metalloproteases Coronavirus viral replication downregulates ACE2, zinc is an essential component of ACE2 receptors, therefore may help to normalise ACE2 receptor function.
  • Vitamin D is an important immune modulator and support lung epithelial tissue, countries which have been most severely affected by COVID-19 are those that have a higher incidence of Vitamin d deficiency as they have just come out of winter and are above 20 degrees latitude in the northern hemisphere.
  • Data shows the possibility that TGG and luteolin may achieve their antiviral activity by interfering with the virus-cell fusion process against SARS-CoV. Quercetin is an analogue of luteolin, which is structurally related, and is FDA approved has additionally demonstrated anti-viral properties potentially via the same mechanism.
  • Curcumin has been shown to modulate the NLRP3 inflammasome therefore helping to prevent the cytokine storm.
  • The gut microbiome plays an essential role in supporting the immune system, 70% of immune tissue is found in the gut.

As with any other intervention, it is important to consider the individual as a whole and therefore use a holistic approach. We know that underlying health conditions hold a greater risk of increasing the severity of the illness and therefore of death. Hence, other pathologies should be supported as well, instead of simply aiming to optimise immune function. Dysfunctions including inflammation, leaky gut, dysbiosis and insulin resistance should all be supported and can help drive pathologies and potential complications of viral infections.

This article aims to collate information of nutrients that have been considered to have the potential to support resistance to infection during this pandemic.

Vitamin C

Vitamin C contributes to immune defence by supporting various cellular functions of both the innate and adaptive immune system. It additionally supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity, thereby potentially protecting against environmental oxidative stress.

Mechanism of action in Immune function: ^1–2

• Stimulates Neutrophils – The exposure of neutrophils to oxidants inhibits their motility, which is related to oxidation of membrane lipids and affects cell membrane fluidity. In order to protect themselves from oxidative damage, neutrophils accumulate millimolar (mM) concentrations of vitamins, resulting in improved cellular motility and migration in response of chemotactic stimuli and, subsequently, in enhanced phagocytosis of microbes.
• Supports lymphocyte production and function – lymphocytes can actively accumulate vitamin C against a concentration gradient. It has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects
• Increases interferon production – proteins that are made and released in response to pathogens like viruses. Bacteria, parasites and cancer cells therefore play an important role as the first line of defence against infections.
• Natural Killer Cells – In clinical studies, vitamin C treatment of healthy subjects promoted and enhanced natural killer cell activities
• Monocytes/macrophages – it has been shown that monocytes contain a high concentration of vitamin C which underlines the regulatory role of this vitamin in monocyte and macrophage functions. In support, an in vitro study revealed that intracellular accumulation of pharmacologic vitamin C concentrations could effectively inhibit apoptotic pathways in human monocytes.
• Improves chemotaxis – the attraction and movement of macrophages to a chemical signal. Chemotaxis uses cytokines and chemokines to attract macrophages and neutrophils to the site of infection, ensuring that pathogens in the area will be destroyed.

Function of vitamin C in viral infections^2,3

• Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements.
• Patients with acute infectious diseases have low circulating vitamin C levels (likely due to metabolic consumption)
• Vitamin C has beneficial immunomodulating properties in patients with viral infections, predominantly by increasing the production of α/β interferons and down-regulating the production of pro-inflammatory cytokines.
• Vitamin C reinforces the maintenance of the alveolar epithelial barrier and transcriptionally upregulates the protein channels (CFTR, aquaporin-5, ENaC, and Na+/K+ ATPase) regulating the alveolar fluid clearance.
• Intravenous vitamin C has been shown to reduce mortality in patients with sepsis induced acute respiratory distress syndrome (ARDS)
• A retrospective cohort study indicated that oral vitamin C reduced the risk of herpes simplex keratitis recurrence particularly in combination with oral antiviral therapy
• Three human controlled trials had reported that there was significantly lower incidence of pneumonia in vitamin C‐supplemented groups, suggesting that vitamin C might prevent the susceptibility to lower respiratory tract infections under certain conditions

Specific Research for vitamin C on COVID-19^3,4,5,6

Note this research has been done on intravenous vitamin C:

Research as emerged that treatment with intravenous vitamin C has potential in reducing inflammation in the lungs and could therefore play a key role in lung injury caused by coronavirus infection

As of 14th February 2020, a randomised controlled trial (RCT) has been undertaken at the Zhongnan Hospital, that aims to evaluate the clinical efficacy and safety of vitamin C in viral pneumonia from SARS-CoV-2. They hypothesise that vitamin C infusion can improve the prognosis of severe acute respiratory tract infections. The treatment arm includes a 12g vitamin C infusion (q12h) for seven days and the primary outcome measures the ventilation-free days.⁷

Zinc

Zinc is involved in multiple aspects of immune function. It is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells and also affects development of acquired immunity.^7,8,9

Zinc deficiency is associated with reduced:

• T cell and B cell function
• Lymphoproliferative response to mitogens
• Thymic hormone levels
• Phagocytosis
• Chemotaxis
• Cytotoxic activities

Zinc deficiency therefore increases susceptibility to infectious diseases.

Function of zinc in viral infections ^9,10,11

Zinc deficiency impairs antiviral immunity, particularly to herpes simplex, common cold, herpes simplex virus, hepatitis C, and the human immunodeficiency virus (HIV). A meta-analysis of oral zinc supplementation studies suggested beneficial effects on the shortening of symptom duration and duration of common cold infection.⁶

It has been shown that intracellular levels of zinc may play a role in prevention of viral infections as increasing levels can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. Other in vitro studies have demonstrated reduced viral replication of viruses including severe acute respiratory syndrome (SARS) coronavirus.

Metallothioneins (MTs) are small, cysteine-rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Metallothionein expression is well documented in the context of viral infection. Antiviral effects of zinc treatment against hepatitis C (HCV) in vitro was mediated through MT induction. Suggesting that zinc may facilitate the antiviral role of MTs against other viruses.

Viruses such as HIV use the enzyme reverse transcriptase to hijack the cell’s DNA in order to replicate, without it the viral genome would not be able to incorporate into the host cell, resulting in failure to replicate. Although coronavirus does not appear to use the same mechanism to enter cells, reverse transcriptase inhibitors have been highlighted as potential candidates for the treatment of COVID-19, with some improvements of symptoms reported.^12,13

Both zinc and manganese have been shown to inhibit reverse transcriptase.

Specific research on Coronaviruses:

Positive-stranded RNA (+RNA) viruses include many important pathogens, including SARS CoV coronaviruses. They have evolved a variety of replication strategies, but are unified in the fact that an RNA-dependent RNA polymerase (RdRp) functions as the core enzyme of their RNA-synthesizing machinery. Coronaviruses utilise the enzyme SARS-CoV RdRp where elongation of which was inhibited and template binding reduced by the presence of zinc in vitro. Zinc ionophore also were demonstrated to block replication of SARS CoV in cell culture (in vitro).^10,11

Research suggests SARS-Cov-2 virus enters cells via ACE2 by binding to zinc metalloproteases Coronavirus viral replication downregulates ACE2, zinc is an essential component of ACE2 receptors, therefore may help to normalise ACE2 receptor function.^14,15

Vitamin D

Vitamin D is known to support healthy immune function and has been shown to be deficient in the majority of the population particularly over the winter months. An interesting correlation has been seen where COVID-19 dominates in the northern hemisphere, which is just coming out of winter when vitamin D levels are known to be reduced. Are also predominant in areas which has latitudes above 20^ON, again associated with reduced vitamin D status. An anomaly to this is Japan, where fatalities are lower, however their diet is rich in sources of vitamin D, especially oily fish.¹⁶

• • The most severe outbreak in the north has been Italy where it is noted vitamin D deficiency is one of the highest in Europe.
  • Japan is an outlier in the north, with only a very mild outbreak and has the lowest incidence of Vitamin D deficiency thanks to its high fish-content diet¹⁴. [NB: Other factors no doubt contribute in both countries but culture and behaviour account for speed of spread not case fatality rates].

Role of Vitamin D in immunity ¹⁷

As the vitamin D receptor is expressed on immune cells (B cells, T cells and antigen presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in a milieu of immunological functions. Vitamin D can modulate both the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection.

Research on efficacy against infections ¹⁸

Vitamin D is known to mitigate the scope of acquired immunity and regenerate endothelial lining. This may be beneficial in minimising the alveolar damage caused in ARDS. Level I evidence showed that there is a 12% overall protective effect of vitamin D supplementation against bacterial and viral acute respiratory tract infection, increasing to 19% in those individuals on the daily or weekly regimen of vitamin D. Furthermore, there is a 70% protective effect when vitamin D deficiency is corrected with supplementation.⁹

Summary of vitamin D3 in relation to COVID-19^19–24

• Research suggests SARS-Cov-2 virus enters cells via ACE2 Coronavirus viral replication downregulates ACE2 dysregulating the renin-angiotensin system (RAS) and leads to a cytokine storm) in the host, causing Acute Respiratory Distress Syndrome (ARDS).
• Research shows that Vitamin D acts to rebalance RAS and attenuates lung injury
• Research shows that Vitamin D supplementation increases immunity and reduces inflammatory responses and the risk of acute respiratory tract infection
• Vitamin D deficiency is strongly associated with ARDS and poor mortality outcomes, as well as being associated with many comorbidities associated with Covid-19 case fatalities.
• High dose oral Vitamin D has been shown to improve mortality in patients with severe vitamin D deficiency.
• Chronic vitamin D deficiency induces lung fibrosis through activation of the RAS.

Vitamin D can be manufactured in sunlight by the skin and obtained from the diet although it can be difficult to get enough from the diet; vitamin D is found in oily fish, butter and eggs. The government recommends supplementing 10ug of vitamin D all year round although requirements may increase depending on vitamin D status.  Public health England have recently increased the recommended level to 25ug/day during the current pandemic

Vitamin A is important for the function of neutrophils, macrophages, and natural killer cells. Deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection. Vitamin A is also required for adaptive immunity and plays a role in the development of T both-helper (Th) cells and B-cells. It is also essential for the maintenance and repair of epithelial tissue and therefore helps to maintain the integrity of the respiratory and gastrointestinal lining.^25,11

Research of Vitamin A and viral infections

Vitamin A deficiency is strongly involved in measles which can become severe in vitamin A‐deficient children. The mechanism by which vitamin A and retinoids inhibit measles replication is upregulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection during subsequent rounds of viral replication.¹¹

The effect of infection with infectious bronchitis virus (IBV), a kind of coronaviruses, was more pronounced in chickens fed a diet marginally deficient in vitamin A than in those fed a diet adequate in vitamin A.

Vitamin A is rich in oily fish, eggs and also as beta-carotene (which can be converted to vitamin A) in orange and yellow vegetables.

Selenium

Studies have demonstrated an enhancement of both cell-mediated and humoral immune responses by increasing levels of selenium intake. Selenium is an essential antioxidant and also supports the production of the master intracellular antioxidant, glutathione. Dietary selenium deficiency that causes oxidative stress in the host can alter a viral genome so that a normally benign or mildly pathogenic virus can become highly virulent in the deficient host under oxidative stress. In the deficient state, the selenium supplementation is helpful for the prevention and treatment of viral infections^11,26

Role in viral infections: ^27–30

• Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses
• In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains
• This suggests that Se-deficiency affects cell-mediated immunity to a greater extent than humoral immunity for anti-influenza viral responses in this model
• The notion that Se “boosts” the immune system has been supported by studies involving ageing immunity or protection against certain pathogens
• Replication of a mild strain of influenza virus in Se-deficient mice results in a novel virulent strain that causes severe lung pathology even when passed into Se-adequate mice
• These studies demonstrated that the Se status of the host can profoundly influence the genome of viral pathogen, leading to a new viral strain. Thus, host nutritional status should be considered when studying the mechanisms underlying the evolution of emerging viruses and may assist in predicting new viral outbreaks and devising new strategies to limit the emergence and spread of these pathogenic forms

Sources of selenium depend on the selenium content of soil and food but can be found in Brazil nuts, oily fish, eggs and seaweed.

Lactoperoxidase^45-56

The inhalation of pathogens is the primary route for infections that affect the respiratory system. Viruses are spread via tiny droplets or particles and have the potential to live on surfaces long enough to penetrate the mucosal epithelium. The epithelium of the respiratory tract provides a physical barrier to viruses and is therefore one of the first lines of defence utilised by the body to ward off infectious agents. This makes innate airway defences crucial in preventing illness from taking hold. An effective defence is reliant on many factors such as communication with the adaptive immune system and the secretion of epithelial defence molecules.

Lactoperoxidase (LPO) is an enzyme that is found in our exocrine secretions and is well known for its antimicrobial activity. Glands that secrete LPO include the mammary, salivary and mucosal glands, thus making LPO present in milk, saliva, tears and the epithelial surfaces of the respiratory and gastrointestinal tract.

Mechanisms of Action in Immune Function

• LPO is a natural antimicrobial agent and one of the body’s first lines of defence against pathogens
• The LPO system is a combination of lactoperoxidase, thiocyanate (or iodine) and hydrogen peroxide and makes up part of the humoral immune response
• The mechanism of action is the oxidation of thiocyanate ions with the use of hydrogen peroxide to form hypothiocyanite ions
• Hypothiocyanite exerts a wide spectrum of activity against bacteria (gram positive and gram negative), viruses, yeasts and moulds. It does so by oxidizing the thiol groups of amino acid residues of microbial proteins, leading to impaired function, inhibition of cell division or death of the microorganism¹
• LPO is present in human milk throughout lactation and contributes to its protection against pathogens
• With regard to oral health, the LPO system regulates the composition of microflora and prevents the growth of pathogenic microorganisms present in periodontitis.
• LPO also plays an important role in protecting the respiratory and digestive tract

How well the innate system functions however, is heavily dependent on our nutritional status and can be compromised if our diet is poor. Nutrients can be tailored specifically to influence the response of the host and the following can help to facilitate LPO.

Iron

LPO is an iron containing glycoprotein and therefore dependent on adequate levels of iron in the body. Iron deficiency is the most common nutritional disorder in the world,therefore having widespread potential implications on innate system competence. Ensuring adequate levels of iron are met can help to optimise LPO.

LPO uses either thiocyanate or iodine as its substrate of which it oxidises.

Thiocyanate is found in plant foods such as kale, cabbage, cauliflower, Brussel sprouts and turnips. It can also be derived from plants containing cyanogenic glycosides such as almonds, linseed and beans. A shift in our dietary patterns over the last few decades towards processed foods and away from natural foods has seen a potential widespread reduction in the consumption of thiocyanate containing foods.

Iodine

Iodine deficiency is common and is often related to poor soil quality and hence lower levels in natural foods or dairy, or where little seafood is eaten. A shift away from natural foods has further caused a decline in the levels of iodine ingested as has less salt consumption (or non-iodized salt). Iodine rich foods include iodized salt, dairy, seafood etc.

LPO

• Hypothiocyanite has powerful anti-viral capabilities as it has been shown to oxidize the sulfhydryl groups often present on the outer structure of viruses rendering them damaged or destroyed
• By oxidizing free thiol radicals of proteins and creating disulfide bonds hypothiocyanite seems capable to alter the surface proteins of respiratory viruses, contrasting their binding with the airway epithelium
• It is also argued that hypothiocyanite might interfere with the synthesis and assemblance of viral proteins and nucleic acids, thereby interfering with the release of viruses from infected cells
• One study showed that the H1N2 influenza virus was inactivated by human and rat tracheal epithelial cells. The LPO system which produced hypothiocyanite showed a potent anti-influenza mechanism which inactivated the virus prior to infection of the epithelium
• More recently, another study showed that LPO was capable of inactivating 12 different influenza strains when tested in vitro
• A recent laboratory experiment also demonstrated that the hypothiocyanite ion inactivated viral activity in vitro against the 2009 H1N1 pandemic influenza virus.
•  Other research also supports LPO and its antiviral capabilities
• The lack of LPO system in nasal and eye secretions of humans may explain the survival and shedding of some bacteria and viruses as influenza from mucosal secretions

Specific research against Coronaviruses

Research findings have shown hypothiocyanite to be an important and active molecule against a range of viruses and an important participant in the antiviral defences of the innate immune system. This may suggest its wider potential application for newly emergent strains such as the SARS-CoV-2.

Lysine ^57-70

Lysine is an essential amino acid and must be included in the diet as the body is unable to synthesise it. It is important for carrying out many roles in the body including ones related to the immune system.

Mechanism of Action in Immune Function

• Amino acids, including lysine, are building blocks for proteins, which are needed for the production of immune cells
• Studies have demonstrated an important role for amino acids in immune responses by regulating: 1 – the activation of T lymphocytes, B lymphocytes, natural killer cells and macrophages; 2 – cellular redox state, gene expression and lymphocyte proliferation; and 3 – the production of antibodies and cytokines
• Research has shown that lysine is capable of strengthening the immune system and exhibits anti-viral properties. It has been shown to have positive effects on the herpetic family of viruses which include Herpes (HSV-1), Epstein Barr and Kaposi’s sarcoma herpesvirus
• L-lysine has shown significant improvement in both the rate and quality of wound healing. Lysine treated wounds showed a remarkable thickening of the dermo-epidermal layer, suggesting increased cell proliferation from the basal layer.
• Regulates inflammatory immune response (inhibits TNF and IFN)
• Lysine can increase the absorption of zinc, and therefore helps support the body’s immunity

Function of Lysine in Viral Infections

Lysine & Arginine

• It is essential to look at the relationship that exists between lysine and arginine to gain a better understating of the function of lysine on viral infection
• Lysine and arginine share the same biological pathway and both compete for entry in to the cell
• Many studies have demonstrated that some viruses rely on arginine for their survival and that arginine is an essential requirement for their replication and progression.
• Lysine is thought to be effective against some viruses as it blocks arginine and hence viral replication
• There are several mechanisms by which lysine functions: it competes with arginine for reabsorption at the renal tubule, thereby increasing arginine excretion; it competes for intestinal absorption; it induces the enzyme arginase, resulting in degradation of arginine; and it competes for transport into cells
• When arginine is not available, herpes viruses are unable to complete a single replication cycle and cell damage is evident in infected cells
• A study showed that Lysine had a positive effect on HSV-1 infection, symptoms and occurrence⁹ and further studies support lysine supplementation on the reduced recurrence rate of HSV-1 infections
• In addition, excess nitric oxide from arginine can become peroxynitrate, which has been shown to increase infection. One study concluded that nitric oxide together with O2 may be the most important pathogenic factors in influenza virus-induced pneumonia in mice
• Another study showed that the severity of the flu virus has been shown to increase with a greater amount of nitric oxide. Lysine is therefore indicated in limiting nitric oxide by regulating arginine
• A decrease in respiratory infections has positively been associated Lysine
• Having sufficient lysine in collagen helps to prevent viruses and bacteria from entering cells

Flavonoids

Flavonoids are an important class of natural products and have several subgroups, which include chalcones, flavones, flavonols, and isoflavones. Flavonoids have many functions besides antioxidant effects and they also have antiviral abilities. ^31,32

Studies have suggested:

• Flavonoids from Pterogyne Nitens could inhibit the entry of the hepatitis C Virus.
• Anti‐coronavirus activity of some flavonoids (Herbacetin, rhoifolin and pectolinarin) was due to the inhibition of 3C‐like protease
• Other flavonoids (Herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside, and helichrysetin) were also found to be able to block the enzymatic activity of MERS‐CoV/3CLpro
• Bioflavonoids from Torreya nuciferaalso brought inhibition effect of SARS‐CoV/3CL (SARS-CoV 3C-like protease (3CLpro) mediates the proteolytic processing of replicase polypeptides functional proteins therefore playing an important role in viral replication)
• Data shows the possibility that TGG and luteolin may achieve their antiviral activity by interfering with the virus-cell fusion process against SARS-CoV. Quercetin is an analogue of luteolin, which is structurally related, and is FDA approved has additionally demonstrated anti-viral properties potentially via the same mechanism.
• Several flavonoids were tested for their potential to regenerate and promote the hypothiocyanite production by LPO with positive results⁵

Cytokine storm

It has been well documented that the severity of COVID-19 is often due to a cytokine storm where inflammation runs away and therefore the body’s own inflammatory response becomes more dangerous than the infection itself. SARS-CoV2 has been shown to activate the NLRP3 inflammasome, which is strongly involved in hyper activation of the innate immune response. The body requires an appropriate inflammatory response to react to initial infection and signal to other parts of the immune system to begin the fight against the infection. Therefore promoting an appropriate inflammatory response is essential. Many people already have a heightened inflammatory response as it is a driver of many chronic conditions (such as cardiovascular disease, autoimmune disorders, dementia and diabetes type 2.), this may contribute to the increased risk of a severe infection due to comorbidities. Many suggested interventions are to normalise the inflammatory response to help support resilience and help to prevent activation of the NLRP3 inflammasome.^33,34

Quercetin

Quercetin has been shown to have antiviral effects against both RNA (e.g. influenza and coronavirus) and DNA viruses (e.g., herpesvirus). Quercetin has a pleiotropic role as an antioxidant and anti-inflammatory, modulating signalling pathways that are associated with post-transcriptional modulators affecting post-viral healing.^11,35,36

Studies have shown quercetin:

• Promotes viral eradication or inactivation – inhibition of viral replication
• Favourably modulate viral-induced pathological cellular processes – Modulation of NLRP3 inflammasome activation
• Mechanistically promote resolution of collateral damage and restoration of function: – Modulation of mast cell stabilization (anti-fibrotic)

Curcumin:

Curcumin has been shown to modulate the NLRP3 inflammasome and a preprint suggests that curcumin can target the COVID-19 main protease to reduce viral replication.^33,37

Microbiota

The diverse intestinal microbiota shapes the immune system and promotes the host well-being. The respiratory tract microbiota also influences the host immune responses to the virus. Acute respiratory viral infections disrupt the host-microbiota interactions and create the intestinal dysbiosis with the post-viral immune responses that contribute to pneumonia development by the secondary bacterial infection. The healthy, diverse intestinal and respiratory tract microbiota is then another critical determinant for supporting immunity.²⁴

Beta Glucans^38–44

Beta glucans are not synthesised by the human body and therefore are recognised as foreign. As they are found in the cell walls of fungi and bacteria the innate immune system recognises them as a potential pathogen, although they themselves do not possess the ability to cause an infection. The recognition of these specific molecules triggers the upregulation of the immune system.

Innate immune cells, unlike acquired immune cells, do not have the ability to recognise a wide range of antigens, however they carry on their surface an extremely important group of receptors called Toll-Like Receptors (TLRs). TLRs only respond to a limited number of compounds; but as these compounds are very basic elements in micro-organisms, and one or more of them occurs in every bacterium, virus and parasite, the TLRs are able to recognise almost any infection and initiate an appropriate immune response. When they recognise a bacterial cell wall compound, for example lipopolysaccharide or a fungal wall compound such as a beta glucan 1-3, 1-6, they initiate an antimicrobial response involving heightened macrophage and dendritic cell activity (when the TLRs are exposed to viral DNA they elicit a different antiviral response). Therefore beta glucans stimulate the body’s own antibiotic reaction and are able to activate the innate immune response. This is because the 1-3 particle exactly fits to the C3 receptor in the innate immune system.

After ingestion, beta glucans are taken up by macrophages in the gut associated lymphoid tissue (GALT) and are phagocytosed (eaten). Macrophages digest the beta glucans into smaller fragments and release these over time into the bloodstream. The fragments bind to receptors on neutrophil granulocytes and NK cells, priming them and making them more active. Neutrophils are involved in killing bacteria, and the NK cells destroy both virally infected cells and cancer cells; leading to increased resistance to infection, and enhanced apoptosis of abnormal cells.

Beta glucans can also evoke a response via the acquired immune system. When innate dendritic cells are activated they communicate the presence of a pathogen to the acquired immune system, warning that an infection is likely, and instruct naïve T helper cells to develop into TH1 cells, which have anti-microbial properties, rather than TH2 cells which are involved in allergic reactions. The resulting increase in the TH1/TH2 ratio has important anti-allergy effects.

Research

• There are increasing problems with antibiotic and anti-viral resistance. Priming the innate immune system with 1-3, 1-6 beta glucan has repeatedly been shown to increase resistance to bacteria and viruses in humans, fish, poultry, Guinea pigs, pigs and honey bees
• A study looking at 49 adults aged 50 to 70 showed that daily oral β-1-3, 1-6 glucan may protect against upper respiratory tract infections (URTIs) and reduce the duration of URTI symptoms in older individuals once infected. This may be linked to effects on innate immune function. Larger studies are needed to confirm the benefits of β-1,3/1,6 glucan on URTIs in this older population
• Beta glucan supplementation maintains immune function in endurance athletes
• Beta glucan supplementation reduces post-exercise URTIs in marathon runners
• A study in healthy subjects showed a 20-25% reduction in common cold episodes with supplementation of yeast beta glucan 1-3, 1-6. It concluded that the yeast beta glucan preparation increased the body’s potential to defend against invading pathogens

Immunity

Some evidence suggests that following infection, immunity to COVID-19 may be reasonably short lived. Is it a novel mechanism of this virus or is it immune dysfunction that inhibits complete immunity? It is not currently known how long immunity may last following COVID-19 infection or if and when a vaccine is administered. However it is important that the immune system maintains its “memory” of previous infections allowing it to produce antibodies effectively in the event of a second infection. Compromised or dysfunctional immunity is more likely to result in a less adequate response to a second infection than if the immune system is primed and ready. Therefore, supporting a healthy immune and inflammatory response is essential for optimising prolonged immunity as much as possible.