A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection

Abstract

Immune support by micronutrients is historically based on vitamin C deficiency and supplementation in scurvy in early times. It has since been established that the complex, integrated immune system needs multiple specific micronutrients, including vitamins A, D, C, E, B6, and B12, folate, zinc, iron, copper, and selenium, which play vital, often synergistic roles at every stage of the immune response. Adequate amounts are essential to ensure the proper function of physical barriers and immune cells; however, daily micronutrient intakes necessary to support immune function may be higher than current recommended dietary allowances. Certain populations have inadequate dietary micronutrient intakes, and situations with increased requirements (e.g., infection, stress, and pollution) further decrease stores within the body. Several micronutrients may be deficient, and even marginal deficiency may impair immunity. Although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection. Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc. Better design of human clinical studies addressing dosage and combinations of micronutrients in different populations are required to substantiate the benefits of micronutrient supplementation against infection.

Keywords: immune system; infection; micronutrients; minerals; vitamins.

Figure 1

Basic components of the immune system, including key micronutrients that contribute to immune function. The schematic highlights the areas of immunity and the micronutrients that affect these functions that are covered in this review. Abbreviations: Ig, immunoglobulins; MHC, major histocompatibility complex.

Figure 2

Micronutrients have key roles at every stage of the immune response [2,7,8,9]. This schematic summarizes important components and processes that are involved in different aspects of the innate and adaptive immune responses. The circles highlight those micronutrients that are known to affect these responses. The significant overlap between micronutrients and processes indicates the importance of multiple micronutrients in supporting proper function of the immune system. Abbreviations: APCs, antigen-presenting cells; C3, complement component 3; CRP, C-reactive protein; Cu, copper; Fe, iron; IFNs, interferons; Igs, immunoglobulins; ILs, interleukins; GI, gastrointestinal; GM-CSF, granulocyte-macrophage colony stimulating factor; MAC, membrane attack complex; MCP-1, monocyte chemoattractant protein-1; Mg, magnesium; MHCs, major histocompatibility complexes; NK, natural killer; NO, nitric oxide; ROS, reactive oxygen species; Se, selenium; TLRs, toll-like receptors; TNF, tumor-necrosis factors; Zn, zinc.

Figure 3

For optimal immune protection and resistance to infection, daily intakes may need to be much higher than the RDAs [24,27]. Abbreviations: RDA, recommended dietary allowance [143]; UL = tolerable upper intake level, the maximum daily intake unlikely to cause adverse health effects.