The Role of Nutrition in the Immune System

Should we pay more attention? Part II of II

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Vitamins and minerals, known as micronutrients, are nutrients needed by our body for optimal function and often required in only small amounts. These micronutrients are not produced in the body and thus must be obtained from our food (CDC, 2020). Micronutrient deficiencies can have devastating outcomes. At least half of children globally under 5 experience vitamin and mineral deficiencies (UNICEF, 2020) and globally 2 million people suffer ‘hidden hunger’. Micronutrient deficiency is often referred to as ‘hidden hunger’ because they develop slowly over time and their impact is often invisible until permanent damage has been done (UNICEF, 2020).

Is food a solution?

A recent article published in the Sight and Life Magazine concluded that nutrient requirements were not met in diets with high stable food consumption as is the case in many low- and middle-income countries (Depford et al, 2019). Many approaches have been adopted with the aim of eliminating micronutrient deficiencies including periodic vitamin A supplementation, iodized salt, targeted iron/folate supplementation, fortified flour, other fortified foods, home fortification with micronutrient powders, and homestead food production. Efforts continue globally to find approaches supporting the eradication of hidden hunger because of the impact deficiencies have on health and survival (Semba, 2012). During times of emergency, as we are currently experiencing with the coronavirus (COVID-19) pandemic, nutrition is of greater importance in order to ensure our immune system operation is optimized to fight such infections.

minerals, immunity, nutrition, immune system, immune response

What to consider? 

In The Role of Nutrition in Immunity: Should we pay more attention? Part 1 of II, we considered the research demonstrating the central role nutrition plays in effective functioning of our immune system. As surmised by Wu and colleagues, “There is little argument that deficiency in both macronutrients and micronutrients causes immune function impairment, which can be reversed by nutrient repletion” (Wu et al, 2019). Also highlighted was the World Health Organization’s (WHO) guidance on the importance of a healthy diet during the current pandemic where it states the crucial role of nutrition for health, particularly in times when the immune system might need to fight back such as is the case during COVID-19 (WHO, 2020). Included in the review was the current research and thinking on the factors that impact our immune system’s ability to fight infection focusing specially on the role of micronutrients. Gombart and colleagues concluded that indeed the complex, integrated immune system requires several micronutrients that have essential, often synergistic roles at every phase of the immune response (Gombart et al, 2020) with even marginal deficiencies impacting our immune response. Based on a variety of systematic and clinical data, vitamins AB6, B12C, D, E, and minerals copper, folateiron, selenium, and zinc (read our Vitamin and Mineral: a brief guide) are particularly important to boosting immune response and we looked specifically at the research supporting the role of vitamins in the immune response. If you have not read Part I already, the blog post can be found here

In this blog we will look specially at folate and the trace minerals thought to have a significant role in the immune system and examine if research backs up these claims.

Copper

After iron and zinc, copper is the most abundant dietary trace mineral. It is a component of many enzymes and is needed to produce red and white blood cells. Copper-dependent enzymes transport iron and load it into hemoglobin, a protein that carries oxygen through the blood. 

Copper-dependent enzymes also provide a natural defense against free radicals that damage the body; manufacture collagen (required by skin and bone); inactivate histamine, which is responsible for allergic reactions; and degrade dopamine into a neurotransmitter so cells can “talk” to each other.  

In a study by Djoko and colleagues they concluded that copper was essential for effective innate immune response and inadequate levels leads to increased susceptibility to bacterial infection (Djoko et al, 2015). Understanding coppers influence on these positive impacts requires further research.

Current advice on supplementation concludes that consuming a balanced diet provides all the necessary nutrition required but where there are challenges in meeting dietary recommendations, supplements are a useful addition in helping meet our nutritional needs (EUFIC, 2020).

Folate (B9)

Folate works together with vitamin B12 to form healthy red blood cells. It is also necessary for normal cell division, the normal structure of the nervous system and specifically in the development of the neural tube (which develops into the spinal cord and skull) in the embryo. Vitamins B6, B12, and folate are involved with maintenance of normal blood homocysteine levels.

While its role in DNA synthesis points to immunity, Dhur and colleagues found that cell-mediated immunity is particularly impacted by inadequate folate status (Dhur et al, 1991). More studies are required to confirm these findings. Mikkelsen and Apostolopoulos writing in the book Nutrition and Immunity did conclude that inadequate levels of folic acid and B12 can change our immune responses through a variety of processes including production of nucleic acid and protein synthesis as well as interfering negatively with the activity of immune cells (Mikkelsen and Apostolopoulos, 2019).

Immune System, Immunity, Folate, Nutrition

Iron

Iron is essential for the formation of hemoglobin in red blood cells; which transports oxygen around the body. Iron also serves as a cofactor to enzymes in oxidation/reduction reactions (i.e., accepts or donates electrons). These reactions are vital to cells’ energy metabolism.

Research suggests low iron levels affects our ability to have an adequate immune response (Gomez and Soyano, 1999). It is required for immune cell production and growth particularly lymphocytes, which are related to the initiation of specific responses to infection (Gomez and Soyaon, 1999).

A study by Dallman concluded that “abnormalities in cell-mediated immunity and ability of neutrophils to kill several types of bacteria’ is commonly seen in iron-deficient patients (Dallman, 1987).

Iron sequestration is an important innate host defense mechanism because many pathogens depend on this essential element. As a consequence, availability of body iron is strictly controlled and bound to proteins such as transferrin and ferritin (Cassat and Skaar 2013).

Iron, Nutrition, Minerals, Immunity, Immune system

Selenium

Selenium is an important component of the body’s antioxidant system, protecting the body against oxidative stress, a natural by-product of the body’s metabolism. There is now considerable evidence that selenium plays a key role in the functioning of the immune system.

This relates to its role in regulating oxidative stress, redox, and other cellular processes in nearly all tissues and cell types, including those involved in innate and adaptive immune responses (Hoffmann et al, 2008).

Interestingly research demonstrates that inadequate selenium status is linked to the incidence, severity, or disease advancement of some viral infections
(Broome et al, 2004 and Guillin et al 2019); Arthur and colleagues when examining selenium and immunity concluded that deficiency can result in the creation of proinflammatory compounds that would influence risk toward diseases such as heart disease and cancer (Arthur et al, 2003).

Zinc

Almost all cells in our body contain zinc, a vital nutrient for growth and development. The highest concentrations are found in muscle, testes and bone. The body tightly regulates zinc levels. Stress and infections for example cause plasma zinc levels to fall. Zinc has a key role as a catalyst in a wide range of reactions and a large number of enzymes. A study by Maret suggests this and he concluded that the human genome encodes up to 3,000 zinc proteins.

Much evidence points to zinc having a strong role in the immune system and wound healing. Research shows that zinc affects multiple elements of the immune system, from the barrier of the skin to gene regulation within lymphocytes (Shankar and Prasad, 1998). Maywald and colleagues reported that both zinc insufficiency as well as excess leads to changes in immune cell numbers and activities, which results in increased susceptibility to infections and development of inflammatory diseases (Maywald et al, 2017). Interestingly, zinc has the ability to reduce oxidative stress which has been shown to help ward off disease.


* Please note these are approximate values and can vary based on recommended reference values employed.
** Criteria for establishing zinc requirements are based on categorizing diets as high, medium and low bioavailability of zinc. For detailed information please refer to WHO Requirements 1998.
*** Iron requirements fluctuate throughout the life course. Iron needs increase during menstruation, pregnancy, and periods of rapid growth such as early childhood and adolescence. Recommended levels are based on bioavailability of iron from certain diets and vary from 15% bioavailability to 5%.
 
References
 
Arthur, JR; McKenzie, RC and Beckett, GJ (2003) Selenium in the Immune System, The Journal of Nutrition, Vol 133 (5), pp:1457S–1459S [Online] Available at: https://academic.oup.com/jn/article/133/5/1457S/4558526 (Accessed on 15th April 2020)
 
Broome, Broome CS; McArdle, F; Kyle, JAM;  Andrews, F; Lowe, NM;  Hart, CA;  Arthur, JR and Jackson,MJ (2004) An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. The American Journal of Clinical Nutrition, Vol 80 (1), pp:154–162 [Online] Available at: https://academic.oup.com/ajcn/article/80/1/154/4690273 (Accessed on 17th April 2020)
 
Cassat JE, Skaar EP (2013). Iron in infection and immunity. Cell Host Microbe. 13(5) pp:509–519. [Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676888/ (Accessed on 21st April 2020)
 
CDC (2020) Micronutrient Facts. [Online] Available at: https://www.cdc.gov/nutrition/micronutrient-malnutrition/micronutrients/index.html (Accessed on 20th April 2020)
 
Dallman, PR (1987) Iron Deficiency and the Immune Response Am J Clin Nutr 46(2):329-34.[Online] Available at: https://pubmed.ncbi.nlm.nih.gov/3303900/ (Accessed on 18th April 2020)
 
Depford, A; Baldi,G; Bose,I; Badham, J; Knight, F;Klemm, and dePee, S (2019) Requirements not Met by Diets High in Staple Foods [Online] Available at:
https://sightandlife.org/wp-content/uploads/2018/12/SALMZ_0218-1.pdf (Accessed on 21st April 2020)
 
Dhur, A and  Galan, P and  Hercberg, S (1991) Folate Status and the Immune System Prog Food Nutr Sci 15(1-2):43-60.[Online] Available at: https://pubmed.ncbi.nlm.nih.gov/1887065/ (Accessed on 17th April 2020)
 
Djoko, KY; Ong, CL Y; Walker, MJ and McEwan, AG (2015) The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens J Biol Chem 290(31): pp18954–18961 [Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521016/ (Accessed on 18th April 2020)

EFSA (2015) Scientific Opinion on Dietary Reference Values for copper. [Online] Available at: https://www.efsa.europa.eu/en/efsajournal/pub/4253 (Accessed on 18th April 2020)

Gombart AF; Pierre A and Maggini S (2020). A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients, Vol 12 (1) [Online] Available at: https://www.ncbi.nlm.nih.gov/pubmed/31963293 (Accessed on 29th March 2020)
 
Guillin, O.M.; Vindry, C.; Ohlmann, T.; Chavatte, L (2019) Selenium, Selenoproteins and Viral Infection Nutrients2019, 11(9), 2101 [Online] Available at: https://www.ncbi.nlm.nih.gov/pubmed/31487871 (Accessed on 21st April 2020)

Hoffmann, PR and Marla J. Berry, MJ (2008) The influence of selenium on immune responses. Mol Nutr Food Res; 52(11): 1273–1280. [Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723386/ (Accessed on 15th April 2020)
 
Maret W (2013) Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr. 4(1)pp:82–91. [Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648744/  (Accessed on 20th April 2020)

Maywald, M; Wessels, I and  Rink, L (2017) Zinc Signals and Immunity Int J Mol Sci 18(10): 2222.[Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666901/ (Accessed on 17th April 2020)

Mikkelsen K., Apostolopoulos V. (2019) Vitamin B12, Folic Acid, and the Immune System. In: Mahmoudi M., Rezaei N. (eds) Nutrition and Immunity. Springer, Cham
 
Shankar ,  AH , and AS Prasad (1998)  Zinc and Immune Function: The Biological Basis of Altered Resistance to Infection Am J Clin Nut 68(2 Suppl):447S-463S. [Online] Available at: https://pubmed.ncbi.nlm.nih.gov/9701160/ (Accessed on 17th April 2020)

Soyano, A and M Gómez M (2008) Role of Iron in Immunity and Its Relation With Infections Arch Latinoam Nutr 49(3 Suppl 2):40S-46S [Online] Available at: https://pubmed.ncbi.nlm.nih.gov/10971835/ (Accessed on 15th April 2020)

Semba RD (2012). The historical evolution of thought regarding multiple micronutrient nutrition. J Nutr 142(1):pp:143S–56S. [Online]Available at: https://pubmed.ncbi.nlm.nih.gov/22157539/ (Accessed on 20th April 2020)

UNICEF (2020) Micronutrients [Online] Available at: https://www.unicef.org/nutrition/index_iodine.html (Accessed on 20th April 2020)

World Health Organization (2020) Food and Nutrition tips during self-quarantine [Online] Available at: http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/novel-coronavirus-2019-ncov-technical-guidance/food-and-nutrition-tips-during-self-quarantine (Accessed on 2nd April 2019)

World Health Organization (2020) WHO launches new global influenza strategy [Online] Available at: https://www.who.int/news-room/detail/11-03-2019-who-launches-new-global-influenza-strategy (Accessed on April 7th 2020)

WHO (1998) Vitamin and mineral requirements in human nutrition Second edition. https://apps.who.int/iris/bitstream/handle/10665/42716/9241546123.pdf?ua=1

Wu D; Lewis E D., Pae M and Meydani Simin N (2019) Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance Frontiers in Immunology  Vol 9 pp 31-60  [Online] Available at: https://www.frontiersin.org/articles/10.3389/fimmu.2018.03160/full (Accessed on 17th April 2020)