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The Effect of Vitamins and Minerals on the Immune System

Abstract: The immune system includes lymphoid organs such as the thymus, spleen, bone marrow, and lymph nodes. The major tasks of this system are to fight disease-causing germs, known as pathogens, and to neutralize harmful environmental substances.​ ​Nutrients, which can enter the body through consumption of food or supplements, affect the immune system’s functions. Nutrients that directly affect the immune system include vitamins A, C, and D and zinc. These nutrients are absorbed by the small intestine and distributed throughout the body through the circulatory system. Insufficient quantities of these nutrients cause the immune system to suffer from reduced innate or adaptive immune responses, which increases susceptibility to infection.


Innate and Adaptive Immunity:

There are two subsystems within the main immune system: the innate, or non-specific, immune system and the adaptive, or specific, immune system. Innate immunity provides a general defense against pathogens and includes the skin, mucus membranes, and macrophages. Adaptive immunity occurs after exposure to an antigen, which can include proteins on the surface of bacteria, fungi, and viruses and involves specialized, systematic cells to fight pathogens. The two adaptive responses are the cell-mediated immune response, where activated T-cells kill off pathogens, and the humoral immune response, where B cells produce antibodies that neutralize pathogens. Together, the two immune systems help the body fend off infections.


Vitamin A and the Immune System:

Vitamins, or vital amines, are organic compounds that are required in the diet because they cannot be sufficiently synthesized by the organism. Vitamin A is the generic name for the group of fat-soluble vitamins that include retinol, retinal, and retinoic acid. The main source of preformed vitamin A include animal-derived foods such as liver, fish, eggs, and milk, and the main source of provitamins that are metabolized to active vitamin A in the body include yellow and leafy green vegetables such as squash and spinach. Vitamin A has been shown to play a role in host resistance to infections, most likely due in part to its ability to stimulate the immune system through unclear mechanisms. Supplementation of vitamin A in preschool children is known to decrease the risks of mortality and morbidity from some forms of diarrhea, measles, human immunodeficiency virus (HIV) infection, and malaria. These effects are related to enhanced antibody production, lymphocyte proliferation, sustainment of the integrity of mucosal epithelia in the gut, and increased T-cell lymphopoiesis. Moreover, vitamin A supplementation in infants can potentially improve the antibody response to tetanus and measles vaccines. However, there is no conclusive evidence for the direct effect of vitamin A supplementation on lymphocyte activation or cytokine production. On the other hand, vitamin A deficiency leads to the replacement of the epithelium lining the upper respiratory passage and urinary tract by keratinizing squamous cells (squamous metaplasia). This loss of the mucociliary epithelium of the airways increases susceptibility to pulmonary infections because epithelium, which covers most inner and outer surfaces of organisms, functions as the front line of defense against pathogen invasion. The recommended intake of vitamin A, or retinol activity equivalents (RAE), per day is 900 μg for men and 700 μg for women.

Vitamin C and the Immune System: Vitamin C is a water-soluble vitamin found in citrus fruits, broccoli, strawberries, and red peppers. Vitamin C is an essential nutrient that cannot be synthesized by humans, so it must be consumed through food or supplements. Severe vitamin C deficiency can lead to scurvy, which weakens collagenous structures and results in poor wound healing and impaired immunity. Vitamin C is an essential micronutrient for the immune system because it is a potent antioxidant, supports epithelial barrier function against pathogens, and enhances differentiation and proliferation of B- and T-cells. Due to its ability to readily donate electrons, vitamin C is a highly effective antioxidant and thus protects important biomolecules such as proteins and carbohydrates from damage by oxidants formed during normal cell metabolism and through external exposure to toxins such as those from cigarette smoke. The skin contains concentrations of vitamin C, with the epidermis having higher levels than the dermis. Since scurvy is characterized by bleeding gums, bruising, and impaired wound healing, vitamin C has been shown to have a role as a cofactor for hydroxylase enzymes that stabilize the tertiary structure of collagen. Vitamin C is also a cofactor for a family of biosynthetic and gene regulatory enzymes. These gene regulatory effects most likely enhance differentiation and proliferation of B- and T-cells. An adequate amount of vitamin C, which would include about 100-200 mg/day, would improve the immune response.


Vitamin D and the Immune System: Vitamin D is a fat-soluble vitamin obtained from the diet in the form of fatty fish such as salmon and mackerel or foods fortified with vitamin D including dairy products and orange juice. Vitamin D is also synthesized in the skin after exposure to UV B light. Its synthesis is influenced by skin pigmentation, latitude, season, and use of sunblock. Vitamin D is known to enhance the function of immune cells such as T-cells and macrophages. Cells of the immune system, including macrophages, dendritic cells, T-cells, and B-cells, express specific enzymes that can hydroxylate vitamin D to act on immune cells in an autocrine or paracrine manner by binding to the vitamin D receptor. Additionally, according to multiple cross-sectional studies, individuals with lower vitamin D levels were more likely to report a recent upper respiratory tract infection than individuals with sufficient levels of vitamin D. Vitamin D deficiency has thus been associated with increased susceptibility to infection, including tuberculosis and other viral and bacterial respiratory infections. Before antibiotics, physicians even used vitamin D and cod liver oil for tuberculosis. There is also increasing evidence linking vitamin D deficiency and autoimmune disease include multiple sclerosis (MS), rheumatoid arthritis, and diabetes mellitus. Inflammation from autoimmune diseases causes the most damage, and vitamin D acts as a natural anti-inflammatory. Vitamin D is an immuno-modulator, so it regulates immune system function. For example, vitamin D normalizes hyperinflammatory conditions during cytokine storms. Moreover, vitamin D is essential in making two antimicrobials called defensin and cathelicidin. Cathelicidin attacks a pathogen’s cell membrane to destroy it, and defensin, which is needed in the mucus membranes. Overall, sufficient vitamin D levels, which would be a level between 20 ng/mL to 50 ng/mL, in an organism mostly obtained from the sun or supplements, decreases susceptibility to infection.


Zinc and the Immune System:

Zinc is a trace mineral primarily found in oysters, red meat, sea foods, and legumes. Zinc is involved in DNA and protein synthesis, wound healing, and thymus function. The thymus is a specialized lymphoid organ of the immune system, where T-cells mature. Zinc assists the thymus gland in producing cytotoxic T-cells, which target and kill pathogens. Zinc also helps the body produce perforin, a chemical that natural killer cells inject into pathogenic cell membranes to destroy the targeted cells. Moreover, zinc reduces inflammation, which leads to a faster healing process. Zinc is also a powerful antioxidant that can prevent oxidative stress from viral infections. Oxidative stress is an imbalance between the production of free radicals and the body’s ability to detoxify their harmful effects through neutralization by antioxidants. In fact, zinc deficiency has been associated with thymic atrophy, which results in a decrease in the number of lymphocytes, preventing the body from effectively fighting off pathogens. Zinc deficiency also results in a defective white blood cell response, which increases the duration of the infection. Thus, sufficient levels of zinc, which is around 11 mg for adult men and 8 mg for adult women, can help the body’s immune system fend off infections through assisting lymphocytes mature and through lowering inflammation levels.


References: Abbas, Abul K., et al. ​Robbins Basic Pathology.​ 9th ed., Elsevier Saunders, 2013. Aranow, Cynthia. “Vitamin D and the Immune System.” ​Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research​, U.S. National Library of Medicine, Aug. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/.

Carr, Anitra and Maggini, Silvia. “Vitamin C and Immune Function.” ​Nutrients​, vol. 9, no. 11, November 2017, pp. 1211. doi: 10.3390/nu9111211 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707683/. Huang, Zhiyi, et al. “Role of Vitamin A in the Immune System.” ​Journal of Clinical Medicine​, MDPI, 6 Sept. 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC6162863/.

Mora, J Rodrigo, et al. “Vitamin Effects on the Immune System: Vitamins A and D Take Centre Stage.” ​Nature Reviews. Immunology​, U.S. National Library of Medicine, Sept. 2008, www.ncbi.nlm.nih.gov/pmc/articles/PMC2906676/. Prasad, Ananda S. “Zinc in Human Health: Effect of Zinc on Immune Cells.” ​Molecular Medicine (Cambridge, Mass.)​, ScholarOne, 2008, www.ncbi.nlm.nih.gov/pmc/articles/PMC2277319/.


BY: Richa Kuklani

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