The Importance of Nutrition to Balance Immunological Response and Reduce Susceptibility to Virulence

Updated: Mar 9


I certainly doubt any of us have escaped being personally affected by the Corona virus and certainly news and updates have been drummed into us on a daily basis as to how we limit spread and prevent infection. This article focuses primarily on the need to address specific nutrient status and common seasonal deficiencies, which when restored, help to ensure a balanced immune response and how these specific nutrient deficiencies may also predispose us to a higher susceptibility of virulence and infections.


Nutritional deficiency or inadequacy can impair immune functions. There is a strong growing body of evidence which suggests that for certain nutrients increased intake above currently recommended levels may help to optimize immune functions, while maintaining tolerance. This article focuses on the nutrients vitamin C, vitamin D, zinc, selenium and B vitamins.


Vitamin C – has been researched many times to assess its ability to reduce lung infections and reduce duration and severity of symptoms of flu, colds and pneumonia (1). This action is partly due to its role in building collagen, modulating inflammation and protection of mucosal linings (think respiratory system, digestive & bladder) as well as its status as an antioxidant. Studies have found that being exposed to high levels of physiological stress (infections, surgery, trauma, burns, sepsis) can significantly change the metabolism of vitamin C leading to faster depletion in serum plasma levels. Research being conducted in patients admitted to ICU due to physiological stress found that it was necessary to give them higher levels of vitamin C in order to raise their plasma levels to the normal range and that addressing deficiency reduced the length of stay in extensive care (2). This indicates that larger doses are required to compensate for the increased metabolism due to the presence of infection or trauma (4g daily). As a preventative dose I would recommend taking 2 grams daily split into 500mg/1g divided over the day for adults and 200-500mg for children (dependent on weight). If you find yourself fighting a virus or infection I recommend increasing to 4-6g daily for adults and 1-2g split over the day for children (2). Good dietary sources of vitamin C are kiwis, red peppers, citrus fruits, green peppers, melons, broccoli, papaya, Brussel sprouts, kale, strawberries, sweet potato, pineapple and mango. Vitamin C is also found in significant amounts within the adrenal glands and needs replenishing in times of stress which helps us to keep our immune response healthier.


Zinc - The trace element zinc is essential for the immune system with deficiency having a direct impact on adaptive and innate immune response, including a reduction in the activity of the thymus and modulation of our T cell functions. Studies have shown that zinc plays an immune-modulating effect on the immune response by ensuring that it does not spiral out of control. Other studies have noted parallels between the decline of immunological function, zinc status and aging. Even a mild deficiency can have an impact as zinc affects many complex biological immunological functions and multiple genetic expressions (3, 4).


So how does zinc work to modulate the immune system: Human cells contain a protein which pulls zinc into key cells where it then plays a vital role in fighting infection and by doing so helps to balance the immune response and dial down inflammation. This is important as too much inflammation, although an integral and vital part of the innate immune response, will not only damage the pathogen but also damage the tissues i.e. the vessels in the respiratory system (3). It is also interesting that some conditions like diabetes tend to have accompanying zinc deficiency. Zinc is an insulin signalling promoter (5).


The recommended *RDA’s for zinc is 12-16mg daily for a male adult and 10-12mg for a woman (6). Zinc supplementation should be taken away from grains to avoid binding to phylates which inhibits absorption and also affects the bioavailability of zinc from plant foods. Loss of appetite, smell and taste can indicate deficiency but there are other signs too. It is advised to get your zinc tested before supplementing and to take a formula with a small amount of copper to prevent imbalances of these two metals. Over-supplementing can cause a suppression of the immune response and too much inhibition of inflammation which is a necessary immunological process. When fighting an active infection you can up the dose to 30-50mg daily.


Ensuring zinc levels are adequate, particularly at the end of winter, is important as this is when we are more likely to be deficient and when viruses tend to hit us harder. Age can also be a contributing factor to deficiency due to the use of medications like diuretics or insufficient nutrient intake. Indeed, deficiencies of immunological modulating nutrients maybe making certain people more susceptible to the replication of Covid-19 (7). Dietary food sources of zinc are oysters, shrimp, beef, lamb, liver, crab, pork, sesame seeds, pumpkin seeds, quinoa, oats, eggs, chicken (dark meat), miso, tofu, mushrooms, kelp, spirulina, avocado, green leafy vegetables, legumes, pulses, cashews, almonds, cheese, yoghurt. It is also added to fortified cereals.


Selenium is another important trace element for human immunity. It plays a crucial role in thyroid and metabolic functions and is integral in the antioxidant defence system and our immunological response. Deficiency is related to increased risk of viral infections, viral virulence and neurological and inflammatory disorders as it not only impairs the host immunity but also the behaviour and virulence of the pathogen (8). Selenium is present in soil and gets into our food through absorption into plant proteins. Over farming and soil depletion of nutrients has been labelled a public health risk as even sub optimal deficiency can have implications for our health (9). It is interesting that China has been given low selenium or selenium deficient status by the World Health Organisation (10). Selenium appears to be a key nutrient in counteracting particular viral infections and deficiency can result in damage to the heart and increased lung pathology when exposed respectively to the Coxsackie virus or pneumonia due to the viruses undergoing virulent genetic changes (11). Selenium is known to influence all parts of the innate and adaptive immune system and is found in large amounts in immune tissues like spleen, lymph nodes and liver (12). Dietary supplementation with selenium has also been shown to improve declining NK cell function in the elderly (13). It is important not to over supplement with selenium as excess can result in gastrointestinal and neurological symptoms. RDA’s are set at 55mcg for both adult men and women with optimal levels set at 250mcg and upper tolerable limits set at 400mcg (14). Certain food types can contain high levels of selenium particularly Brazil nuts (dependent on soil) so caution should be taken when consuming large amounts over a space of time. For example, according to the U.S. Department of Agriculture Food Composition Database, Brazil nuts have 544 mcg selenium per ounce (6-8 nuts), but values can differ (15). Breast milk, formula, and food should be the only sources of selenium for infants (14). Other good sources of selenium are brown rice, soybeans, kelp, garlic, mushrooms, pineapple, onions, tomatoes, broccoli, sardines, prunes, turkey, salmon, spinach, organ meats, grains, eggs, lentils, cottage cheese and chicken.


Vitamin D – commonly referred to as our ‘sunshine hormone’, vitamin D has been shown to be an important regulator for our immune response and deficiency appears to be correlated with an increased susceptibility to infection as well as autoimmunity (16). One large study looking at 19,000 cohorts with findings taken over 6 years (1988 to 1994) concluded that those with levels lower than 30ng/dl were more likely to report a upper respiratory infection, even taking into account variables such as age, gender, climate and BMI (16). Multiple studies have reported this same increase in respiratory complaints, tuberculosis, influenza and other infections with sub-optimal levels of vitamin D (<30ng/dl ) (18,19). A study conducted in 2007 showed that the phagocytic (to engulf) function of macrophages is increased in those who received vitamin D supplementation (20). Other positive immunological effects of vitamin D are; it lowers production of pro-inflammatory immune mediators some of which are responsible for acute inflammatory cytokine storms (IL-21, IL-1, IL-6, IL-8, IL-12 and TNFα) whilst enhancing production of anti-inflammatory mediators (21); it shifts the reaction away from the inflammatory Th17 phenotype (implicated in autoimmunity) and facilitates the induction of T regulatory cells which help to keep the immune system in check (22) and it stimulates the expression of antimicrobial peptides (AMPs), present in neutrophils, monocytes, natural killer cells and epithelial cells of the respiratory tract, helping to inhibit viral, bacterial and fungi infiltration (23).

Fig 1: Aranow C. (2011). Vitamin D and the immune system


In humans, the majority of our vitamin D is created in the skin through exposure to UVB and a small part is metabolized through our diet (oily fish like salmon, mackerel, sardines, trout, fish liver oils) or mushrooms exposed to light (24). Small amounts are also found in liver, cheese and egg yolks. This means we are reliant on endogenous production which can be affected by factors such as clothing, use of sunscreen, skin pigmentation, climate, genetics and our nutritional habits (25).


So how much vitamin D do we need to support our immunological fitness and what level makes us deficient? Sun exposure for 20 minutes on legs, arms, face and/or torso without sunscreen can give us quite a big dose of vitamin D during the warmest of the summer months but this can be variable due to factors like inadequate exposure, time of day, pollution, latitude, BMI, pigmentation, cultural dress and age (26) and deficiency is actually quite common even in warm countries (27). UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not metabolize vitamin D (28).


The measurement of serum 25(OH) D is considered the most accurate marker for vitamin D status. Levels can be also affected by variants such as whether you are taking medications, for example, cholesterol lowering drugs, anti-seizure meds or corticosteroids (which reduce calcium absorption and affect the metabolism of vitamin D) (29, 30); age and/or menopause, as declining hormones affect the shunting and storage of calcium into the bones; or a decline in intestinal absorption levels or hepatic (liver) or kidney health (31, 32). So taking this all into account what should we be aiming for?


15 to 30 minutes of unprotected sun exposure two to four times a week is generally recommended to maintain adequate serum levels. However, due to the reasons described above and that particularly in the northern hemisphere, there may not be sufficient UVB radiation to consistently synthesize vitamin D, some foods i.e. milk, infant formula, margarine have been fortified to take this shortfall into account, but again the amounts are not very likely to optimise serum levels effectively. Vegans and vegetarians can commonly be deficient unless they consume plenty of these fortified foods and get a fair amount of sun exposure (33).


In 2011, The Endocrine Society issued clinical practice guidelines, stating that to enhance the effect of the vitamin on calcium uptake and use, skeletal, muscle metabolism the serum level of 25(OH)D should be >75 nmol/L (>30 ng/ml) which is about 1,500-2,000 IU/day of supplemental vitamin D for adults, and about 1,000 IU/day in children and adolescents (34). This level tallies with the results of the immunological studies and increased risk of infection above.


Vitamin D toxicity doesn’t occur with sun exposure due to conversion of excess D3 to inactive metabolites but toxicity (although rare) can be induced with high consistent doses of oral supplementation (>10,000 IU/d) for prolonged periods in patients with normal gut absorption or who may be taking excessive amounts of calcium. Most patients with vitamin D toxicity have levels greater than 150ng/mL (35). If serum levels are below 30ng/dl which is about 75nmol/l then raising the level to 40 to 50ng/dl (100-125nmol/L) is considered an optimal and safe upper limit. A recommended amount is 4000-5000IU’s daily to address an insufficiency (this dose also applies to pregnancy and breastfeeding women) (30). Ideally, larger doses should be applied weekly by healthcare practitioners when addressing deficiency and once the desired level is reached, a maintenance dose of 2000IU’s is usually set. If you are getting a lot of sun exposure in the summer (20 minutes without sunscreen), stop taking the supplemental form and start again when the colder seasons arrive. A good time to check your status is at the end of March and before winter sets in. It is important to get your level tested and a recommendation for testing is given below (product guide). However, February and March in the UK is the time vitamin D stores in the liver tend to be low and many of us can be insufficient (<30ng/dl) or deficient (<20ng/dl) so taking a supplemental form to raise levels to >40ng/dl is very important for our immune response and our ability to fight viral infections at this time of year (36).


As vitamin D is a fat soluble nutrient, those who have an inflammatory condition for example like celiac, Crohn’s or ulcerative colitis or who have had gastric bypass surgery will find better absorption with liquid formulations and there are vegan formulas available too (37). Ingesting with some fat will ensure better absorption and combining it with vitamin K will allow for better mineralisation in the skeletal matrix (38). Vitamin K is found naturally in leafy greens like kale, broccoli, cabbage and fermented foods like cheese, yoghurt, natto, eggs and meat and is also produced by bacteria within the colon (39).

Fig 2: Health Practitioner’s Guide to Prescribing Vitamin D and Calcium. Consultant360. Volume 54 - Issue 3 - March 2014


Vitamin D also plays a role in balancing commensal and pathogenic microbiota in the gut some of which release compounds to strengthen the gut barrier and support immune defence. Beta carotene, vitamins B6, folate and B12 also play a role (40).


There is evidence that it plays an important part in regulating the renin-angiotensin system by alleviating lipopolysaccharide (a potent inflammatory molecule) induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), by inducing ACE2/Angiotensin activity and inhibiting renin and the ACE/Angiotensin II/AT1R cascade, which helps to modulate the inflammatory response and the associated cytokine storm, increased alveolar capillary membrane and lung edema (41, 42).


B Vitamins – We are unable to make vitamin B’s so dietary intake is important. B12 has been shown to be an immune modulator and deficiency leads to low numbers of lymphocytes and impairment of the activity of natural killer (NK) cells (43). B6 also plays a similar role, with deficiency affecting both humoral and cell-mediated immune responses including the differentiation and maturation of lymphocytes and antibody and cytokine production via its role in protein synthesis (44). Clinical folate deficiency also results in impaired immune responses, primarily affecting cell-mediated immunity. Correcting these deficiencies has been shown to restore these immune functions (45). Vitamin B1, B2, B3, B5, B7 and B12 also play important roles in our Citric Acid (energy) cycle and are vital for healthy methylation, cardiovascular and neurological function.


Food Sources:


Folate (B9) - Mushrooms, nuts, whole grains, broccoli, asparagus, beans, lettuce, spinach, beet greens, sweet potatoes, leafy greens, avocado, beef liver, beets, brussel sprouts, grains, beans, root vegetables, salmon, turnips, whole grains, white beans.


Vitamin B12 - Beef liver, shellfish, cod, yoghurt, eggs, fish, salmon, sardines, tuna, herring, red meat.


Pyridoxine (B6) - Bananas, avocados, whole grains, cantaloupe, walnuts, soybeans, peanuts, pecans, kale, broccoli, chard, cabbage, spinach, green peppers, carrots, sunflower seeds, pistachio nuts, tuna, turkey, pork, blackstrap molasses, brown rice, melon, chicken, cod, collard greens, beef, flaxseeds, garlic, red bell peppers, salmon, snapper, spinach, strawberries, turnip greens.


B vitamins are water-soluble so any excess is generally excreted in urine. This means they are typically safe at doses much higher than the RDA, but they require a more consistent intake than the fat soluble vitamins (A, D, E).


Optimal supplemental ranges are

B6 – 50mg/d for adults

Folate - 200-400ug for adults

B12 – 50-100ug for adults


*RDA’s is the average daily level of intake that is necessary to avoid clinical or subclinical deficiency in the majority of a healthy general population.


Resources


Products to buy:


Cytoplan – when ordering create an account and apply voucher code CYT23676-10 to get my practitioner’s discount in the shopping basket before proceeding to checkout


Vitamin D - https://www.cytoplan.co.uk/catalogsearch/result/?q=VITAMIN%20d

Vitamin C - https://www.cytoplan.co.uk/catalogsearch/result/?q=Vitamin%20C

Zinc - https://www.cytoplan.co.uk/zinc-copper

Immune Supportive Formulas - https://www.cytoplan.co.uk/health-creation-max-immune

Kids Formulas - https://www.cytoplan.co.uk/kid-s-immunovite

Selenium - https://www.cytoplan.co.uk/selenium

Antioxidant Support - https://www.cytoplan.co.uk/coq10-antioxidant-a-c-e-50mg-coq10

B vitamins – https://www.cytoplan.co.uk/catalogsearch/result/?q=b%20vitamins

Multi’s- https://www.cytoplan.co.uk/wholefood-multivitamin-mineral-120-capsules

https://www.cytoplan.co.uk/catalogsearch/result/?q=cyto%20gold – also suitable for children aged 5 and over

Children’s Multi’s - https://www.cytoplan.co.uk/catalogsearch/result/?q=childrens%20multi


Biocare – when ordering create an account and apply my practitioner referral code P10477 into your account to get my practitioner’s discount.


Vitamin D - https://www.biocare.co.uk/ingredients/vitamin-d/ - includes infant, kid’s and vegan formulas

Vitamin C - https://www.biocare.co.uk/ingredients/vitamin-c/

Zinc - https://www.biocare.co.uk/ingredients/zinc/

Immune Supportive Formulas - https://www.biocare.co.uk/immune-intensive-7-sachets

https://www.biocare.co.uk/mineral-complex

Kids Formulas - https://www.biocare.co.uk/catalogsearch/result/?cat=0&q=childrens+formulas

Selenium - https://www.biocare.co.uk/catalogsearch/result/?cat=0&q=selenium

Antioxidant Support - https://www.biocare.co.uk/microcell-nutriguard-plus

B Vitamins - https://www.biocare.co.uk/catalogsearch/result/?cat=0&q=b+vitamins

Multi - https://www.biocare.co.uk/catalogsearch/result/?cat=0&q=mult


Diagnostic Testing – Regenerus Labs

Vitamin D – £43.50 (Blood spot home test)

Essential Fatty Acids - £96 (Blood spot home test)


If you are interested in getting advice on how to support yourself, dietary choices or would like to order/get more details on good quality nutrient immune supportive products to optimize health then contact me on info@naturohealthnutrition.co.uk for further information. Targeted supplementation can be helpful to counter micronutrient deficiencies and provide enhanced immune support.


Remember to invest in your health at this time. -


References

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3) 2013. Zinc helps against infection by tapping brakes in immune response, February 7, ScienceDaily, Ohio State University. https://www.sciencedaily.com/releases/2013/02/130207131344.htm

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23) T. T. Wang, F. P. Nestel, V. Bourdeau, et al. (2004). Cutting edge: 1,25-Dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. Journal of Immunology, vol. 173, no. 5, pp. 2909–2912

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25) Plotnikoff GA Minn. (2009). Weather or not: the importance of vitamin D status monitoring and supplementation. Med. 2009 Nov; 92(11):43-6.

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27) Khoja SO, Khan JA, Berry JL, Maimani AR, Woolf AD, Lanham-New SA. Nutritional influences on bone in Saudi Arabian women: widespread vitamin D deficiency Presented at the 6th International Symposium on Nutritional Aspects of Osteoporosis; Lausanne, Switzerland; May4-6, 200

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30) https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#en71

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37) Triantafillidis JK, Vagianos C, Papalois AE. (2015). The role of enteral nutrition in patients with inflammatory bowel disease: current aspects. Biomed Res Int. 2015:197167. doi:10.1155/2015/197167 38) Koshihara Y1, Hoshi K. (1997).Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res. 1997 Mar;12(3):431-8 39) Maresz K. (2015). Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integrative medicine (Encinitas, Calif.), 14(1), 34–39. 40) Takiishi T, Fenero C, Câmara, N. (2017). Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers, 5, e137320 41) Jeffery LE, Burke F, Mura M, et al. (2009).1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 183:5458–5467. 42) Kong J, Zhu X, Shi Y, et al. (2013). VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system. Mol Endocrinol. 27:2116–2125. 43) Tamura J, Kubota K, Murakami H, et al. (1999). 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 xp Immunol. Apr;116(1):28–32.

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