Table 3.

Impact of micronutrient deficiency and supplementation on immune responses and the risk of infection.

Micronutrient	Impact of Deficiency	Impact of Supplementation
Vitamin C	Increased oxidative damage [104] Increased incidence and severity of pneumonia and other infections [71,104] Decreased resistance to infection and cancer, decreased delayed-type hypersensitivity response, impaired wound healing [49]	Antioxidant properties protect leukocytes and lymphocytes from oxidative stress [14] Older people: possible reduction in incidence and duration of pneumonia [71] Children: reduced duration and severity of common cold symptoms [105]; improved outcomes in pneumonia, malaria and diarrheal symptoms [9]
Vitamin D	Increased susceptibility to infections, especially RTI [71] Increased morbidity and mortality, increased severity of infections, reduced number of lymphocytes, reduced lymphoid organ weight [49] Increased risk of autoimmune diseases (e.g., type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis) [14]	Reduced acute respiratory tract infections if deficient [71]
Vitamin A	Affects many immune functions, including number and killing activity of NK cells, neutrophil function, macrophage ability to phagocytose pathogens, growth and differentiation of B cells, decreasing number and distribution of T cells, etc. [14] Increased susceptibility to infections (e.g., diarrhea, RTI, measles, malaria) [14,71]	Children: Reduces all-cause mortality, diarrhea incidence and mortality, and measles incidence and morbidity in deficient children (6 month to 5 years) [14,71]; decreased risk of morbidity and mortality from infectious diseases [77] Not beneficial in pneumonia [14]
Vitamin E	Deficiency rare in humans [49] Impairs both humoral and cell-mediated aspects of adaptive immunity, including B and T cell function [14]	Older people: reduced RTI [71]
Vitamin B6	Lymphocytopenia, reduced lymphoid tissue weight, reduced responses to mitogens, general deficiencies in cell-mediated immunity, lowered antibody responses [49]
Vitamin B12	Depressed immune responses (e.g., delayed-type hypersensitivity response, T-cell proliferation) [49] *
Folate	Depressed immune responses (e.g., delayed-type hypersensitivity response, T-cell proliferation) [49] *
Zinc	Decreased lymphocyte number and function, particularly T cells, increased thymic atrophy, altered cytokine production that contributes to oxidative stress and inflammation [14] Increased bacterial, viral and fungal infections (particularly diarrhea and pneumonia) [71] and diarrheal and respiratory morbidity [49] Increased thymic atrophy and consequent risk of infection [97]	Restoration of thymulin activity, increased numbers of cytotoxic T cells, reduced numbers of activated T helper cells (which can contribute to autoimmunity), increased natural killer cell cytotoxicity, reduced incidence of infections [14] Children: reduction in duration of diarrhea and incidence of pneumonia in at-risk children >6 month, but not in children 2–6 month [71]; reduced duration and severity of common cold symptoms [108]; improved outcomes in pneumonia, malaria and diarrheal symptoms [9]
Iron	Reduced capacity for adequate immune response (decreased delayed-type hypersensitivity response, mitogen responsiveness, NK cell activity), decreased lymphocyte bactericidal activity, lower interleukin-6 levels [49]	May enhance or protect from infection with bacteria, viruses, fungi and protozoa depending on the level of iron [71] May theoretically enhance immunity to infectious diseases, but untargeted supplementation may increase availability of iron for pathogen growth and virulence and increase susceptibility to malaria and bacterial sepsis in particular [71] Children: potential detrimental effects in iron-replete children [14]
Copper	Abnormally low neutrophil levels [14] Potentially increased susceptibility to infection [14]	Children: increased ability of certain white blood cells to engulf pathogens if deficient [14] Reduced antibody production in response to influenza vaccine with chronic high doses in healthy young men [14]
Selenium	Impaired humoral and cell-mediated immunity [14] Increased viral virulence [14,71] Suppression of immune function, increased cancer incidence and cardiomyopathy with chronic deficiency [49] Children: increased risk of respiratory infections in the first 6 weeks of life [71]	Improves cell-mediated immunity and enhances immune response to viruses in deficient individuals, but may worsen allergic asthma and impair the immune response to parasites [14]

* Immune system effects of vitamin B12 deficiency and folate deficiency are clinically indistinguishable [49]. RTI, respiratory tract infections.