You cannot go far at the moment without hearing about coronavirus and its impact on our immune system. With cases set to rise and the impact on the country’s infrastructure now becoming of significant concern, it is important that we as individuals take responsibility for our own health.
Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases. Common signs of infection include respiratory symptoms, fever, cough, shortness of breath and breathing difficulties. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death. COVID-19 is the most recent form of coronavirus which is responsible for the current epidemic. The WHO has recently stated that the virus is a pandemic and therefore we all need to be vigilant about avoiding infection as much as possible.1
As has been stated in the media, most individuals infected with the virus will only experience mild symptoms, however there is an increased risk for the elderly, those with underlying health conditions and immunocompromised people. Avoidance, self-isolation and good hygiene, especially hand-washing are all essential methods to help avoid infection as well as help to prevent the spread of the virus. However, individuals with a robust immune system more likely to only have mild symptoms and recover quickly. Therefore, interventions which can help to support normal immune function can be a useful way of helping to protect health.
This week’s blog looks at how viruses infect the body, the role of the immune system in fighting these viruses and the latest research surrounding the protective properties of beta glucans.
How do viruses infect the body?
Individual viruses work in slightly different ways but in simple terms they enter the body from the environment through the respiratory tract, eyes or breaks in the skin and attach to a host cell. They then inject their genetic material into the cell where it can replicate and produce more viruses which then break free and go on to infect other cells. This is known as the lytic cycle – explained below:2
- A virus particle attaches to a host cell.
- The particle releases its genetic instructions into the host cell.
- The injected genetic material recruits the host cell’s enzymes.
- The enzymes make parts for more new virus particles.
- The new particles assemble the parts into new viruses.
- The new particles break free from the host cell.
The immune system is a complex network of cells and proteins and provides the body’s defence mechanism against infections and viruses. The immune system has a number of responses to fend off these viruses and is essential in stopping he lytic cycle.
Role of the immune system
Once a cell has become infected it should be invisible to the immune system as it obviously looks like a ‘self’ cell. Cells overcome this by expressing a protein complex known as class I major histocompatibility complex proteins (MHC class I) which display protein fragments of the virus, which allows then to be recognised by the immune system.3,4
A number of different aspects of the immune system are involved in the initial reaction in order to fend off the infection these include;
Cytotoxic T-Cells – kill cells that are infected with viruses with toxic mediators. Cytotoxic T-cells have specialised proteins called T cell receptors (TCRs) which can recognise a particular antigenic peptide bound to an MHC molecule, they then release cytotoxic factors to kill the infected cell and, therefore, prevent survival of the invading virus.
Natural killer cells – Some viruses can prevent the expression of MHC complexes, in these cases the immune system has a further back up plan with natural killer (NK) cells. When a NK cell finds a cell displaying fewer than normal MHC molecules it releases toxic substances to kill in the infected cell.
Cytokines – when a cytotoxic cell detects a virus’ infected cell it releases cytokines including interferon-g and tumour necrosis factor-a, and transfer a signal from the T cell to the infected, or other neighbouring cells, to enhance the killing mechanisms and stimulate apoptosis.
Interferons – virally infected cells produce and release small proteins called interferons, which play a role in immune protection against viruses and also signal to other immune cells and neighbouring cells.
Antibodies – are produced following infection therefore there is a lag time in the production following infection. Viruses can also be removed from the body by antibodies before they get the chance to infect a cell. Viruses that are bound to antibodies are unable to infect cells, antibodies also stimulate other phagocytosing immune cells to destroy the virus.
If innate immunity is healthy and already primed then it is more prepared for defence against viral infections. One molecule that has been shown to help prime normal immunity is beta glucan here we look at how they function and research behind them.
What are they?
Beta glucans are an important structural component of cell walls in certain organisms such as bacteria, fungi and some plants. They come in different forms depending on the linkages between the monosaccharide (sugar) molecules. The numbers quoted before beta glucans refer to which carbon in the sugar ring the bond is formed between.
For example in beta glucan 1-3 linkages there is a bond between the 1st carbon on one molecule and the 3rd carbon on another. Without getting bogged down in the biochemistry, this is important because research suggests that beta glucan with 1-3 and 1-6 linkages (referred to as beta glucan 1-3, 1-6), which can be found in the cell wall of a fungi known as Saccharomyces cerevisiae (also known as baker’s yeast), elicits the most potent effect on immune function when compared to other beta glucans with 1-3, 1-4 linkages (these are found in oats for example).5,6 This is because the 1-3 particle exactly fits to the C3 receptor in the innate immune system.
How do they work?
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.7
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.8,9,10
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.10
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.11,12
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.9
Intensive exercise, whilst excellent for health in many ways, is associated with reduced immune function due to increased cortisol release (an immune suppressor). Infections, particularly of the upper respiratory tract (URTIs), are common for endurance athletes. UTRIs are also significant in immunocompromised individuals particularly the elderly. Studies have shown that:13
- 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.9
Research shows that beta 1-3, 1-6 glucans extracted from Saccharomyces cerevisae (baker’s yeast) can mitigate symptoms of the common cold. A placebo-controlled, double-blind study published in the Journal of Sports Science and Medicine investigated the effect of beta glucan supplementation on susceptibility to symptoms of URTIs two- and four weeks post marathon. They reported that after two weeks, 68% of the placebo group reported URTI symptoms, while only 32% (250mg) and 24% (500mg) of those taking beta glucan felt symptoms. After four weeks this dropped to 8% for both beta glucan groups versus 24% of placebo subjects.13
While 1-3, 1-4 beta glucans can be sourced through the diet, 1-3, 1-6 beta glucans are often supplemented to achieve therapeutic levels. Studies have demonstrated positive immunomodulatory effects using doses between 50-500mg, with doses between 100-500mg showing greatest effect.14 other studies have suggested 5mg/kg/day as a preventative dose and 10mg/kg/day therapeutically.
Mechanism of action of 1-3, 1-6 glucan from Saccharomyces cerevisiae:
- When consumed orally 1-3, 1-6 glucan from is Saccharomyces cerevisiae taken up in the body by the Peyer’s Patches in the intestines.
- Immune cells called macrophages (located in the Peyer’s patches) ingest 1-3, 1-6 glucan and travel to the immune organs throughout the body.
- Macrophages break down 1-3, 1-6 glucan into smaller fragments that bind to neutrophils, the most abundant immune cells in the body.
- Primed by 1-3, 1-6 glucan neutrophils move more quickly to recognize and kill foreign challenges.
- Studies tracked fluorescently dyed 1-3, 1-6 glucan as immune cells transported it throughout the body. Within days, 1-3, 1-6 glucan is carried to the spleen, bone marrow and other immune organs.
- A study observed significant improvement in the killing activity of immune cells. Phagocytic cells, which literally engulf and destroy foreign challenges, showed greater microbial killing action in subjects who had taken 1-3, 1-6 glucan.17
- The majority of animal and human studies have not uncovered any adverse effects from taking beta glucan. A 14-day animal study found no observed adverse effect of 2,000mg/kg body weight of insoluble beta glucans. The safety of yeast derived beta-glucan supplementation has further been reviewed and supported by EFSA in doses between 375-600mg per day4,15
Yeast allergy: beta glucan supplements should be safe in the case of a yeast allergy. During preparation, the isolates are purified from Saccharomyces cerevisiae (baker’s yeast) and so there are not enough yeast proteins left to cause an allergic reaction16
You can also find more information on working through the coronavirus crisis and the challenges of working remotely from the director of The AIM Foundation, Nic Marks.
You can read this blog here – Working through the Coronavirus Crisis.
- Viral infections are of significant current concern with avoidance, isolation and hygiene methods such as handwashing being essential interventions to help prevent the spread viruses, specifically COVID-19. Supporting innate immunity can be an additional useful intervention to help protect health.
- Our own innate immune system has multiple interventions to enable us to fight off viral infections and in healthy individuals with robust immunity duration and severity of infections are reduced and could be prevented.
- 1-3/1-6 beta glucans from saccharomyces cerevisiae possess immune supporting properties and have been used traditionally for providing immune support.
- Beta glucans have been shown to have an immune boosting effect on T cells, natural killer cells, cytokine production and antibody reaction all of which are involved in the prevention and fight against viruses.
- 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.11
- 1-3/1-6 Beta glucans have been demonstrated to prevent and reduce duration of upper respiratory tract infections in older adults.
If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.
firstname.lastname@example.org, 01684 310099
Helen Drake and the Cytoplan Editorial Team
- Coronavirus (COVID-19) events as they happen. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen. Accessed March 11, 2020.
- Cohen FS. How Viruses Invade Cells. Biophys J. 2016;110(5):1028-1032. doi:10.1016/j.bpj.2016.02.006
- Immune responses to viruses | British Society for Immunology. https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/immune-responses-viruses. Accessed March 11, 2020.
- Noss I, Doekes G, Thorne PS, Heederik DJ, Wouters IM. Comparison of the potency of a variety of β-glucans to induce cytokine production in human whole blood. Innate Immun. 2013;19(1):10-19. doi:10.1177/1753425912447129
- Ikeda Y, Sunakawa T, Okamoto K, Hirayama A. Beta 1,3-Glucan Toxicology Studies Glucan Source: Yeast Citation Abstract.
- Scientific Opinion on the safety of “yeast beta -glucans” as a Novel Food ingredient. EFSA J. 2011;9(5):2137. doi:10.2903/j.efsa.2011.2137
- McIntosh M, Stone BA, Stanisich VA. Curdlan and other bacterial (1→3)-β-d-glucans. Appl Microbiol Biotechnol. 2005;68(2):163-173. doi:10.1007/s00253-005-1959-5
- Chan G, Chan W, Sze D. The effects of β-glucan on human immune and cancer cells. J Hematol Oncol. 2009;2(1):25. doi:10.1186/1756-8722-2-25
- Auinger A, Riede L, Bothe G, Busch R, Gruenwald J. Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects. Eur J Nutr. 2013;52(8):1913-1918. doi:10.1007/s00394-013-0492-z
- Chen J, Seviour R. Medicinal importance of fungal β-(1→3), (1→6)-glucans. Mycol Res. 2007;111(6):635-652. doi:10.1016/j.mycres.2007.02.011
- Stier H, Ebbeskotte V, Gruenwald J. Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan. Nutr J. 2014;13:38. doi:10.1186/1475-2891-13-38
- Jung K, Ha Y, Ha S-K, et al. Antiviral Effect of Saccharomyces cerevisiaebeta-glucan to Swine Influenza Virus by Increased Production of Interferon-gamma and Nitric Oxide. J Vet Med Ser B. 2004;51(2):72-76. doi:10.1111/j.1439-0450.2004.00732.x
- Talbott S, Talbott J. Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes. J Sports Sci Med. 2009;8(4):509-515. http://www.ncbi.nlm.nih.gov/pubmed/24149590. Accessed November 1, 2018.
- Ulbricht C. An evidence-based systematic review of beta-glucan by the natural standard research collaboration. J Diet Suppl. 2014;11(4):361-475. doi:10.3109/09286586.2014.975066
- Kernodle DS, Gates H, Kaiser AB. Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]-beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound infection. Antimicrob Agents Chemother. 1998;42(3):545-549. http://www.ncbi.nlm.nih.gov/pubmed/9517930. Accessed March 11, 2020.
- Virginio Agostoni C, Bresson J-L, Fairweather-Tait S, et al. Suggested citation: EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the safety of “Yeast beta-glucans” as a Novel Food ingredient Scientific Opinion on the safety of “yeast beta-glucans” as a Novel Food ingredient 1 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA J. 2011;9(5):2137. doi:10.2903/j.efsa.2011.2137
- WellImmune research update Jan 2020