Winter is closing in, the days are becoming chillier and shorter, and more time is spent indoors, inevitably bringing us into closer contact with others and the disease-causing organisms they may be harbouring. Now more than at any other time of the year we depend on our immune systems to keep us healthy. What can science tell us about keeping our immune systems in tip top shape, ready to fight off those seasonal bugs?
First of all… what is the immune system? (1)
The human immune system is akin to having our own army within, always on high alert and ready to protect us from a myriad of threats, most of them so small that we cannot even see them. The invaders include tiny pathogens such as viruses, bacteria, protozoa, fungi and parasites as well as toxins from the environment and even the body’s own cells that have been altered by an illness such as cancer.
Unlike most body organs, the immune system is not an isolated group of cells tucked into a corner of the abdomen. On the contrary, it is a complicated network of cells, tissues, organs and processes spread throughout the body but working together to fight off the intruders that can make us ill. A healthy immune system very readily differentiates our own cells from those that are foreign to us and then
works hard to get rid of them.
Our first line of defence is the skin, a physical barrier very capable of keeping many foreign substances out of our bodies. Next are the mucous membranes that line the bodily systems that directly contact the outside world, namely our respiratory, digestive, urinary and reproductive tracts and the borders of our eyes. These membranes can trap microbes and other dangerous particles, ushering some of them out of the body using secretions such as tears, saliva and mucous along with invader-fighting enzymes that can break down cell walls of microorganisms. Yet, even before these preliminary mechanisms have failed, a complex communication system among the various elements of the immune system will be directing white blood cells to prepare for battle by multiplying and travelling to the endangered area.
White blood cells (leukocytes) are the “big guns” of the immune system. They come in two general types – phagocytes and lymphocytes. Phagocytes (neutrophils, monocytes, macrophages and mast cells) surround and absorb pathogens to break them down. Lymphocytes exist in three types – B-cells, T-cells and natural killer cells. B-cells produce antibodies against specific antigens (threats) so the body can “remember” previous invaders and recognize them if they return. T-cells migrate to the thymus and become the “detectives” that recognize “self” from “non-self” and are then sent out to destroy the threatening cells. Natural killer cells are highly specialized lymphocytes with the ability to recognize stressed cells even in the absence of antibodies or other markers, resulting in a much faster immune reaction.
White blood cells constantly circulate through body tissues inside both the blood vessels that carry blood to every corner of our bodies and the lymph vessels that link together the diverse portions of the immune system. White blood cells are also stored in “lymphoid organs” which are distributed throughout the body. The primary lymphoid organs are the bone marrow where all white blood cells are formed and the thymus, sited just below the neck, where T-cells are “trained” to recognize foreign antigens. Secondary lymphoid organs are the spleen, situated in the upper left abdomen; the tonsils and adenoids within the neck; and Peyer’s patches in the small intestine. These organs filter body fluids to trap foreign substances and also provide another storage site for white blood cells as well as a place where the cells can interact with antigens during an immune response. Last but not least are the lymph nodes and their connecting lymphatic vessels situated strategically all through the body. They deliver white blood cells to where they are needed and also transport bacteria and dead or damaged cells to the lymph nodes for disposal.
The gastrointestinal system is our main contact point between the external world and our inner body. It is assaulted many times every day with elements we ingest that have the potential to threaten our health. No wonder there are so many immune cells in the gut. In fact almost 70% of the entire immune system is located in gut-associated lymphoid tissue. Peyer’s patches are lymph-node-type tissues located in the mucosal membrane lining our intestines. They protect the mucosa against infection by releasing both T-cell and B-cell lymphocytes. Other solitary lymphocytes, known as intraepithelial lymphocytes or IELs, are scattered within spaces between the epithelial cells of the intestinal mucosa. These “soldiers” along with the beneficial microorganisms present in the gut flora keep pathogens from being absorbed and causing illness (2).
How can the immune system be boosted?
As you can see the human immune system is not a single entity but a diverse web of specialized cells and organs. Research on its complexities and connections is still in its infancy. However, ongoing investigations are revealing that healthy lifestyle factors show strong positive links with immune function. The following are current recommendations for promoting healthy immune function (3);
Eat a diet high in fruits and vegetables (4,5,6,7,8,9,10).
Exercise moderately and regularly. Studies on exercise show that it can improve antibody response to influenza vaccine, however too much exercise can have the opposite effect (11,12,13).
Maintain a healthy weight (14).
Don’t smoke (15).
If you drink alcohol, drink in moderation (16).
Get adequate sleep (17).
Minimize stress (18).
Avoid infection by using preventative methods such as washing hands frequently and cooking meats thoroughly (19).
When it comes to diet, studies show that nutrient deficiencies can severely impair immune function (52). On the other hand, eating the right nutrients can strengthen it.
Phytonutrients (flavonoids, beta-carotene and folate), vitamins (A, B6, B12, C, D, E), trace elements (iron, selenium and zinc) and soluble fiber all have the ability to boost immune function.
A 2005 review examined the ways in which a lack of adequate micronutrients, especially zinc, selenium, iron, and the antioxidant vitamins (Vitamin A, Vitamin C and Vitamin E), can lead to clinically significant immune deficiency and infections in children (20).
A comprehensive review of phytonutrients found them to have significant antiviral properties that can decrease respiratory tract infections and maintain and modulate immune function (21,22).
Vitamin A shows a broad range of immune effects such as lymphocyte activation and proliferation and increased production of specific antibodies (23).
Vitamin B6 deficiency can inhibit lymphocyte proliferation and weaken immunity (24).
Vitamin B12 increases the activity of immune cells and acts as an immunomodulator for cellular immunity (25).
Vitamin C supports the intestinal membrane function against pathogens and can enhance the activity of immune system cells. Vitamin C also increases the activity of phagocytes such as neutrophils and it can enhance the proliferation of B- and T-cell lymphocytes. Vitamin C deficiency results in impaired immunity and higher risk for infections (26).
Vitamin D supplementation can decrease respiratory tract infection by 12% (27).
Vitamin E is strongly antioxidant and has shown to be capable of enhancing production of T-cells in response to infections. One study of nursing home residents showed that a daily vitamin E supplement resulted in fewer upper respiratory infections compared to those taking a placebo (28)
Iron can inhibit the growth and virulence of microbial pathogens, an important factor in the immune system’s defense against infections (29).
A 2017 meta-analysis looked at 25 studies encompassing over 11,000 individuals and showed that
selenium metabolites can inhibit cancers by increasing cancer cell death and inhibiting angiogenesis, the production of the blood vessels required to feed a tumour and keep it growing (30).
Zinc can balance the immune response by decreasing inflammation from microbial infection and regulating the immune response (31). Studies also show that zinc can improve T-cell function (53).
Soluble fiber, found in foods such as apples, citrus fruits, strawberries, carrots, oats, nuts, seeds, beans and lentils and once thought to exert its benefits only in promoting gut health, has now shown beneficial effects on the immune system through production of short-chain fatty acids (32).
What evidence is available regarding beneficial effects of diet on the immune system?
Simply consuming five servings a day of fruits and vegetables improves antibody responses (4).
A study from Germany followed men eating four different diets in succession. The first two weeks they cut out most of the fruits and vegetables, the next two weeks they consumed tomato juice daily, the third two weeks they drank carrot juice daily and the last two weeks they ate daily dried spinach. During the first two weeks of low fruits and vegetables immune function was decreased but during the succeeding six weeks, immune function increased significantly (9).
High fat diets are associated with reduced immune responses (5,6).
On the other hand, low-fat high-carbohydrate diets enhance the immune system (7).
A study from the late 1980s reported that meat-eaters and plant-eaters did not differ in the total number of white blood cells in their circulation, however the natural killer cells in the plant-based group were about twice as active as those in the meat-eating group (8).
A study from Northern Ireland randomized a group of adults into two groups; one group continued eating their customary low intake of two servings per day of fruits and vegetables and the other group increased their fruit and vegetable intake to five servings a day. After 12 weeks, vaccinations were administered. The antibody response to the vaccines in the group eating five daily servings of fruits and vegetables was significantly higher than in the group eating only two servings. Antibody response to vaccination is a direct indication of the robustness of an immune system (10).
What foods are showing the most promise as immune system boosters?
VEGETABLES
Cruciferous Vegetables
Cruciferous vegetables can regulate the function of IELs, the lymphocytes located between the epithelial cells of the membrane lining the intestines (33). Cruciferous vegetables include kale, broccoli, Brussels sprouts, collard greens, mustard greens, Chinese cabbage, bok choy and kohlrabi. In addition, cruciferous vegetables are an abundant source of antiinflammatory phytonutrients such as flavonoids, beta-carotene, lutein, zeaxanthin, folate and vitamins A, C, E and K as well as the trace mineral selenium.
Legumes
Beans and lentils are healthy sources of soluble fiber and zinc.
Onions
Onions are high in flavonoids, including red/purple anthocyanins and the yellow flavanol known as quercetin. Onions have a wide range of health effects including anticarcinogenic, antiplatelet, antithrombotic, antiasthmatic and antibiotic effects (34).
Garlic
Though garlic has been known for centuries for its health-giving attributes, its active ingredient, Allium sativum, was identified relatively recently. Garlic appears to enhance the immune system through stimulation of lymphocytes, macrophages and natural killer cells (35).
A double-blind randomized placebo-controlled study in 2016 looked at the effect of aged garlic extract on colds and the flu and found that, though the number of illnesses was not significantly different, their severity was significantly reduced in the garlic eating group compared to placebo (36).
Red bell peppers are rich in Vitamin C and the phytonutrient beta-carotene.
Orange and dark green vegetables such as sweet potatoes, carrots, squash and green leafy vegetables because they are high in Vitamin A.
FRUITS
Berries
Many berries (strawberries, raspberries, blackberries and pomegranates) contain ellagic acid which has antioxidant, antitumour, antiallergic, anti-inflammatory, antibacterial and antiviral activities. A 2015 study looked at molecules that mediate immune function and discovered that the presence of ellagic acid multiplies these mediators, increasing immune function (37).
In 2013 the phytonutrients in fruits were analyzed for their ability to boost natural human immunity and the most potent immune modulating chemicals were pterostilbene in blueberries and resveratrol in red grapes (38).
More recently a 2018 review examined studies of the health effects of berries on the digestive tract. It was determined that berries support the immune system and the beneficial microbiota of the intestine and can reduce the number and size of pre-malignant and malignant growths. These beneficial effects were observed primarily from whole berry extracts not individual components of berries (39).
Berries such as blueberries, blackberries, raspberries and strawberries are good sources of flavonoids which are adept at neutralizing oxidants, the harmful waste products of cell processes and can decrease the incidence of upper respiratory tract infections by 33% (40).
Citrus Fruits
Citrus fruits are extremely high in Vitamin C, a potent antioxidant that supports the immune system in a variety of ways (26).
Citrus fruits are also good sources of phytonutrients.
Apples
Apples are abundant in soluble fiber. In 2010 a study demonstrated that mice fed soluble fiber showed “profound, positive changes in their immune system” with fewer symptoms from a bacterial illness and a much faster recovery compared to those fed insoluble fiber (42).
Apples are also an abundant source of phytonutrients that can lower risk of infection and disease (43).
WHOLE GRAINS
A 2017 study found a link between whole grains and a healthy immune system. Participants ate either a diet plentiful in whole grains or one of refined grains only. After six weeks the quantity of memory T-cells was increased. Memory T-cells are specialized lymphocytes that remember past invaders and are primed for a fast defense should they return (44).
Whole grains such as oats and barley are high in beta-glucans (see nutritional yeast) and also a great source of zinc and in selenium.
SEEDS AND NUTS
Seed and nuts are good sources of zinc, Vitamin E and soluble fiber.
Sunflower seeds are a high source of Vitamin B6 and Vitamin E.
Sesame seeds are especially rich in the minerals copper, calcium, magnesium, zinc and iron, all of which are required for healthy immune function.
Brazil nuts are a good source of selenium.
OTHER FOODS
Green Tea
EGCG (epigallocatechin gallate), a polyphenol phytonutrient component of green tea, shows a powerful ability to increase the number of regulatory T-cell lymphocytes that can suppress autoimmune disease and improve immune function (45). Green tea also contains flavonoids which show significant reductions in risk of a cold or flu (40).
Mushrooms
White button mushrooms can improve immunity at mucosal surfaces such as the mouth and the respiratory tract (41). Other mushroom types such as Reishi and Shiitake are showing promise against viruses and some cancers (46). A 2015 study followed participants eating Shiitake mushrooms for 4 weeks and noted improved immunity through greater immune cell proliferation and activation (47).
Many varieties of mushrooms including shiitakes can activate macrophages, lymphocytes and natural killer cells and show anticancer activity and suppression of allergy and autoimmune disease (48).
Nutritional Yeast
Nutritional yeast and brewers’ yeast are excellent sources of insoluble beta-glucans that possess potent immunological effects. A 2014 review concluded that beta-glucans derived from dietary yeast are able to activate and strengthen the human immune system by enhancing macrophage and natural killer cell function. Beta-glucans also show anticarcinogenic activity by inhibiting angiogenesis, the production of blood vessels essential for the long-term viability of a tumour (49,50).
A 2013 placebo-controlled double-blind randomized trial of 162 healthy participants found that those consuming 900 mg daily of brewers’ yeast had 25% fewer cold symptoms than those in the placebo group (51).
SOURCES:
1 https://www.merckmanuals.com/en-ca/home/immune-disorders/biology-of-the-immune-system/overview-of-the-immune-system
2 Vighi, G., Marcucci, F., Sensi, L., Di Cara, G., Frati, F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008 Sep; 153(Suppl 1): 3–6.
3 https://www.health.harvard.edu/staying-healthy/how-to-boost-your-immune-system
4 Edgar, J.D., Gibson, A., Neville, C.E., Gilchrist, S.E.C.M. Increased fruit and vegetable consumption improves antibody response to vaccination in older people: the ADIT study. Proc. Nutr. Soc. Oct 2009; 69(OCE3) – 3rd Immunonutrition Workshop, Girona, Spain.
5 Barone, J., Hebert, J.R., Reddy, M.M. Dietary fat and natural-killer-cell activity. Am J Clin Nutr. 1989 Oct;50(4): 861-867.
6 Yaqoob, P. Monounsaturated fats and immune function. Proc Nutr Soc. 1998 Nov; 57(4):511-520.
7 Santos, M. Immunological effects of low-fat diets with and without weight loss. J Am Coll Nutr. 2003 Apr; 22(2):174-182.
8 Malter, M., Schriever, G., Eilber, U. Natural killer cells, vitamins, and other blood components of vegetarian and omnivorous men. Nutr Cancer. 1989;12(3):271-278.
9 Watzl, B., Bub, A., Brandstetter, B.R., Rechkemmer, G. Modulation of human T-lymphocyte functions by the consumption of carotenoid-rich vegetables. Br J Nutr. 1999 Nov;82(5):383-389.
10 Gibson, A., Edgar, J.D., Neville, C.E., Gilchrist, S.E., McKinley, M.C., Patterson, C.C., Young, I.S., Woodside, J.V. Effect of fruit and vegetable consumption on immune function in older people: a randomized controlled trial. Am J Clin Nutr. 2012 Dec; 96(6):1429-1436.
11 Kohut, M.L., Cooper, M.M., Nickolaus, M.S., Russell, D.R., Cunnick, J.E. Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. J Gerontol A Biol Sci Med Sci. 2002 Sep; 57(9):M557-562.
12 Kohut, M.L., Arntson, B.A., Lee, W., Rozeboom, K., Yoon, K.J., Cunnick, J.E., McElhaney, J. Moderate exercise improves antibody response to influenza immunization in older adults.Vaccine. 2004 Jun 2;22(17-18):2298-306.
13 de Araújo, A.L., Silva, L.C., Fernandes, J.R., Matias, M.de S, Boas, L.S., Machado, C.M., Garcez-Leme, L.E., Benard, G. Elderly men with moderate and intense training lifestyle present sustained higher antibody responses to influenza vaccine. Age (Dordr). 2015 Dec;37(6):105.
14 Viardot, A., Samaras, K. The Effects of Weight Loss and Gastric Banding on the Innate and Adaptive Immune System in Type 2 Diabetes and Prediabetes. J Clin Endocrin Metab. April 2010; 95(6): 2845-2850.
15 Qiu, F., Liang, C.-L., Liu, H., Zeng, Y.-Q., Hou, S., Huang, Lai, X., Dai, Z. Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? Oncotarget. 2017 Jan 3; 8(1): 268–284.
16 Sarkar, D., Phil, D., Jung, M.K., Wang, H.J. Alcohol and the Immune System. Alcohol Res. 2015; 37(2): 153–155.
17 Besedovsky, L., Lange, T., Born, J. Sleep and Immune Function. Pflugers Arch. 2012 Jan; 463(1): 121–137.
18 Segerstrom, S.C., Miller, G.E. Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry. Psychol Bull. 2004 Jul; 130(4): 601–630.
19 Aiello, A.E., Coulborn, R.M., Perez, V., Larson, E.L. Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis. Am J Public Health. 2008 Aug; 98(8): 1372-1381.
20 Cunningham–Rundles, S., McNeeley, D.F., Moon ,A. Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol. 2005; 115:1119–1128.
21 Naithani, R., Huma, L.C., Holland, L.E., et al. Antiviral activity of phytochemicals: a comprehensive review. Mini Rev Med Chem 2008; 8:1106-1133.
22 Gupta, C., Prakash, D. Phytonutrients as therapeutic agents. Complement Integr Med. 2014 Sep;11(3):151-169.
23 Mora, J.R., Iwata, M., von Andrian, U.H. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008 September ; 8(9): 685–698.
24 Qian, B., Shen, S., Zhang, J., Jing, P. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations. J Immunol Res. 2017; 2017: 2197975.
25 Tamura, J., Kubota, K., Murakami, H., Sawamura, T., Matsushima, T., Tamura, T. Saitoh, T., Kurabayshi, H., Naruse, T. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol. 1999 Apr; 116(1): 28–32.
26 Carr, A.C., Maggini, S. Vitamin C and Immune Function. Nutrients. Nov 2017; 9(11).
27 Martineau, A.R., Jolliffe, D.A., Hooper, R.L., Greenberg, L., Aloia, J.F., Bergman, P., Dubnov-Raz, G., Esposito, S. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15; 356:i6583.
28 Meydani, S.N., Leka, L.S., Fine, B.C., Dallal, G.E., Keusch, G.T., Singh, M.F., Hamer, D.H. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004 Aug 18; 292(7): 828-836.
29 Cherayil, B.J. Iron and immunity: immunological consequences of iron deficiency and overload. Arch Immunol Ther Exp (Warsz). 2010 Dec; 58(6): 407–415.
30 Hagemann-Jensen, M., Uhlenbrock, F., Kehlet, S., Andresen, L., Gabel-Jensen, C., Ellgaard, L., Gammelgaard, B., Skov, S. The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D. J Biol. Chem. Nov, 2014; 289: 31576-31590.
31 Liu, M.-J., Bao, S., Gálvez-Peralta, M., Pyle, C.J., Rudawsky, A.C., Pavlovicz, R.E., Killilea, D.W., Li, C., Nebert, D.W., Wewers, M.D., Knoell, D.L. ZIP8 Regulates Host Defense through Zinc-Mediated Inhibition of NF-κB. Cell Reports Feb 2013; 3(2): 386-400.
32 Sherry, C.L., Kim, S.S., Dilger, R.N., Bauer, L.L., Moon, M.L. et al. Sickness behaviour induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-04 and Th21 polarization. Brain, Behaviour and Immunity May 2010. Doi: 10.1016/j.bbi.2010.01.015.
33 Li, Y., Innocentin, S., Withers, D.R., Grigorieva, E.F., Wilhelm, C., Veldhoen, M. Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation. Cell Oct 2011; 146(3): 629-640.
34 Griffiths, G., Trueman, L., Crowther, T., Thomas, B., Smith, B. Onions—A global benefit to health.
Phytotherapy Research Nov 2002; 16(7): 603-615.
35 Arreola, R., Quintero-Fabián, S., López-Roa, R.I., Flores-Gutiérrez, E.O., Reyes-Grajeda, J.P., Carrera-Quintanar, L., Ortuño-Sahagún, D. Immunomodulation and anti-inflammatory effects of garlic compounds. J Immunol Res. 2015; 2015: 401630.
36 Percival, S.S. Aged Garlic Extract Modifies Human Immunity. J Nutr. 2016 Feb; 146(2):433S-436S.
37 Promsong, A., Chung, W.O., Satthakarn, S., Nittayananta, W. Ellagic acid modulates the expression of oral innate immune mediators: potential role in mucosal protection. J Oral Pathol Med. 2015 Mar;44(3):214-221.
38 Guo, C., Sinnott, B., Niu, B., Lowry, M.B., Fantacone, M.L., Gombart, A.F. Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids. Molecular Nutrition and Food Research March 2014; 58(3): 528-536.
39 Govers, C., Kasikci, M.B., van der Sluis, A.A., Mes, J.J. Review of the health effects of berries and their phytochemicals on the digestive and immune systems. Nutrition Reviews Jan 2018; 75(1): 29-46.
40 Somerville, V.S., Braakhuis, A.J., Hopkins, W.G. Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis. Adv Nutr. 2016 May; 7(3): 488–497.
41 Jeong, S.C., Koyyalamudi, S.R., Pang, G. Dietary intake of Agaricus bisporus white button mushroom accelerates salivary immunoglobulin A secretion in healthy volunteers. Nutrition. May 2012; 28(5): 527-531.
42 Sherry, C.L., Kim, S.S., Dilger, R.N., Bauer, L.L.,Moon, M.M., Tapping, R.I., Fahey, G.C., et al. Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization. Brain, Behavior, and Immunity. May 2010; 24(4): 631-640.
43 Boyer, J., Hai, R. Apple phytochemicals and their health benefits. Nutr J. 2004; 3: 5.
44 Karl, J.P., Meydani, M., Barnett, J.B., Vanegas, S.M., Goldin, B., Kane, A., Rasmussen, H., Saltzman, E., et al. Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women. Amer J Clin Nutr March 2017; 105(3): 589–599.
45 Wong, C.P., Nguyen, L.P., Noh, S.K., Bray, T.M., Bruno, R.S., Ho, E. Induction of regulatory T cells by green tea polyphenol EGCG. Immunol Lett. 2011 Sep 30;139(1-2):7-13.
46 Suarez-Arroyo, I.J., Rosario-Acevedo, R., Aguilar-Perez, A., Clemente, P.L., Cubano, L.A. et al. Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models. PLoS One. 2013; 8(2): e57431.
47 Xiaoshuang, D., Stanilka, J.M., Rowe, C.A., Esteves, E.A., Nieves Jr., C., Spaiser, S.J. Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults. Journal of the American College of Nutrition Apr 2015; 34(6): 478-487.
48 Lull, C., Wichers, H.J., Savelkoul, H.F.J. Antiinflammatory and Immunomodulating Properties of Fungal Metabolites. Mediators Inflamm. 2005 Jun 9; 2005(2): 63–80.
49 Stier, H., Ebbeskotte, V., Gruenwald, J. Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan. Nutrition Journal. 2014; 13:38
50 Akramiene, D., Kondrotas, A., Didziapetriene, J., Kevelaitis, E. Effects of beta-glucans on the immune system. Medicina (Kaunas). 2007;43(8): 597-606.
51 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. Dec. 2013; 52(8): 1913-1918.
52 Chandra, R.K. Impact of nutritional status and nutrient supplements on immune response and incidence of infection in older individuals. Ageing Res Rev. Jan, 2004; 3(1): 91-104.
53 Barnett, J.B., Dao, M.C., Hamer, D.H., Kandel, R., Brandeis, G., Wu, D., Dallal, G.E., Jacques, P.F., Schreiber, R., Kong, E., Meydani, S.N.. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2016 Mar;103(3):942-951.