TABLE 6.
Effects of micronutrient supplementation on immune function and vaccine responses (human studies)1
| Type of malnutrition and type of immune function | Effects of supplementation on immune system (reference) |
| Vitamin A | |
| Epithelial barrier function | ● High-dose VAS above 6 mo of age decreases risk of death from infections such as measles and diarrheal diseases (290) |
| ● VAS in the context of HIV infection or lower respiratory tract infections has been associated with adverse outcomes (105, 263, 290–292) | |
| ● Improved barrier function (105) | |
| ● Abnormal dual-sugar (lactulose, mannitol) intestinal permeability inversely correlated with serum retinol (293) and partially normalized by supplementation in VA-deficient individuals in some studies (294) but not others (295, 296) | |
| ● Increased symptomatology after high-dose VAS during acute lower respiratory tract infections reported in some studies (105) may indicate restored mucus production | |
| Innate physiologic barriers | ● VAS did not affect CRP, SAA, and/or AGP concentrations among children with subclinical or clinical VAD (297–299) |
| ● CRP and AGP did not change in men with low VA stores given VA (300) | |
| Macrophage function | ● Increased monocyte numbers (301) |
| ● Decreased TNF-α concentrations in children (301) but the opposite in men (106) | |
| ● Decreased IFN-γ concentrations in children (302) but not in pregnant women (303) | |
| ● Increased IL-10 concentrations in children (105, 301) but no or an opposite effect in adults (106, 303, 304) | |
| Neutrophil function | ● Neutrophil phagocytosis of latex beads increased in VA-deficient children given a single dose of VA (305) |
| ● Neutrophil phagocytosis of E. coli did not change in men with low VA stores given VA (300) | |
| NK cell function | ● An increase in NK cells in HIV-infected children supplemented with VA (105) |
| ● NK cell numbers did not change in men with low VA given supplemental VA; however, there was a positive correlation between VA stores and peripheral blood NK cells (300) | |
| T cell function | ● Increased lymphocyte counts, particularly CD4 counts (105) |
| ● CD4:CD8 ratios were increased or unchanged by supplementation (306) | |
| ● Increase in naive CD4 T cells after supplementation; higher memory CD8, CD45RO (307) | |
| ● Higher mitogen-induced IL-2, IL-4, and TNF in response to supplementation (106) | |
| B cell function | ● Supplementation had no overall effect on measles vaccine response (308) and a negative response in individuals with baseline high titers (103) |
| ● No overall effect on oral polio vaccination | |
| ● Supplemented children increased IgG1 responses to DTP, minor IgG3 response, no change in IgG2 and IgG4 (309) | |
| ● No overall effect on BCG vaccine in VA-supplemented children, lower response in VA-supplemented boys at 2 mo (310) | |
| ● Increased antibody responses to some vaccines (measles vaccine by 9 mo of age, oral polio vaccine, type 1, hepatitis B vaccine, rabies vaccine) (103) | |
| ● Short-term diminished cellular response to PPD in boys (103) and hospitalized children (105) | |
| Zinc | |
| Epithelial barrier function | ● Zn supplementation in children led to an improvement in the lactulose:mannitol excretion ratio in some (311) but not other (312, 313) studies; ratio may improve in infected children without Zn deficiency given supplemental Zn (314) |
| Innate physiologic barriers | ● Zn-supplemented children had higher serum complement C3 (315) |
| NK cell function | ● Children with diarrhea supplemented with Zn supplementation do not exhibit an increase in NK cells (316) |
| ● Increased NK cell activity in the elderly (317) | |
| T cell function | ● Increased CD4+ cell count in AIDS patients (318) |
| ● Increased thymocyte count in thymus (319) | |
| ● Increased thymulin activity (320) | |
| ● No consistent effect of Zn supplementation on DTH to TB antigen [reviewed in (103)] | |
| B cell function | ● No effect of Zn supplementation of mothers on BCG response in children (321) |
1
AGP, α1-acid glycoprotein; BCG, bacille Calmette-Guérin; CD, cluster of differentiation; CD45RO, cluster of differentiation antigen 45 RO; CRP, C-reactive protein; DTH, delayed-type hypersensitivity; DTP, diphtheria tetanus-pertussis; PPD, purified protein derivative; SAA, serum amyloid A; TB, tuberculosis; VA, vitamin A; VAD, vitamin A deficiency; VAS, vitamin A supplementation.