We observed that elderly nursing home residents with low serum zinc concentrations at the end of one year of 50% RDA micronutrient daily supplementation, including zinc, had a higher risk of pneumonia and longer duration of pneumonia episodes as well as increased antibiotic use and longer duration of antibiotic use for treatment of pneumonia episodes. In addition, low baseline concentrations of serum zinc in our elderly nursing home population were associated with increased all-cause mortality.
Our finding of a significantly lower all-cause mortality rate (by 39%) between those with normal versus low baseline serum zinc concentrations among elderly in this study suggest that zinc may play a crucial role in influencing mortality in the elderly. Severe zinc deficiency can impair immunity and increase susceptibility to infectious diseases, a major cause of mortality in the elderly (1
). Indeed, the risk of mortality was reduced by 27% in participants of the Age-related Eye-Disease Study (aged 55 to 81 years) who received zinc supplements (RR: 0.73; 95% CI, 0.61−0.89) (31
). In addition, zinc supplementation has been shown to reduce overall mortality by as much as 51% in children with diarrhea and 68% in infants born full-term and small for gestational age (32
When baseline serum zinc status was used as a measure of zinc to determine if low serum zinc affects susceptibility to pneumonia, differences failed to reach statistical significance. It may be that findings using baseline zinc concentrations were attenuated due to the higher risk of death among subjects with low baseline zinc concentrations or due to loss of subjects from serious illnesses and/or hospitalizations. In addition, because all study participants were provided with ½ RDA supplement that included zinc, the baseline concentrations may not reflect zinc status during much of the study period.
Because of the potential bias introduced by zinc supplementation, we performed similar analyses using final zinc concentrations, as this measure may better reflect the zinc status of subjects during the course of the study. We observe a strong association between low final zinc concentrations with increased incidence and duration of pneumonia, as well as total and duration of antibiotic use for pneumonia treatment. As described in the results, the effects observed were specific to zinc and were not observed with other micronutrients. Furthermore, the lower incidence and morbidity of pneumonia observed in subjects with normal final zinc concentrations compared to those with low final zinc concentrations were not due to differences between the two groups in changes in weight, BMI, or other micronutrients (19
) during the study period.
Zinc deficiency has been suggested to be a risk factor for immune deficiency and subsequent infection relapses in the elderly (12
). Zinc is essential for membrane integrity, DNA synthesis and cell proliferation, in addition to being a cofactor to more than 300 enzymes (5
It is essential for all highly proliferating cells in the human body, especially the immune system (36
). Thymus atrophy and lymphopenia, as well as other defects in T cell function have been observed in both zinc deficiency and in the elderly (2
Low zinc consumption has been reported in the elderly (10
). Bogden et al. reported that zinc ingestion was below the RDA in more than 90% of their 100 study subjects aged 60−89 years (37
). In addition, as mentioned above, we found below normal serum zinc concentrations in approximately 30% of the nursing home elderly enrolled in our vitamin E supplementation study. This level of deficiency persisted during the study period despite giving the participants supplements with ½ RDA of zinc (19
). Thus, our finding of a significant association between low serum zinc level and pneumonia could be of major importance to the health of elderly, as poor zinc status would lead to impaired immune response, which could in turn result in increased susceptibility to infections in the elderly (9
). Supplementing with ½ RDA of zinc appeared to benefit many of the subjects with inadequate baseline zinc concentrations, but the results also showed that this supplementation was not adequate to maintain serum zinc concentrations in a significant proportion of subjects.
Plasma or serum zinc concentrations are also known to decrease sharply in many infections (35
). The decline is part of a set of metabolic reactions to infection known as the acute phase response (40
). Although one could argue that lower serum zinc concentrations might be due to a higher incidence of pneumonia, this is unlikely to be the case here as the acute effect of pneumonia on zinc is likely to be transient--approximately 2 weeks if effective therapy is provided (41
). Given the similar incidence of pneumonia in our participants in the last months of the study, transient suppression of serum zinc by the acute phase response is unlikely to be responsible for the low end study zinc concentrations.
Zinc supplementation may play an important role in the prevention and/or modulation of infectious diseases in the elderly (3
). Various studies on zinc supplementation in the elderly have observed increased circulating zinc concentrations (13
), as well as enhanced immune status including improved cell-mediated immune response, serum thymulin activity, and IL-2 production, and increased response to skin-test antigens (12
). Also, when cultures of white blood cells from elderly subjects were supplemented with 15 μM zinc (the physiologic concentration), they produced interferon-alpha in amounts comparable to those from the younger subjects (43
). In a randomized, double-blind, placebo-controlled clinical trial (N=81), institutionalized elderly had a significant decrease in the mean number of respiratory infections 2 years following supplementation with micronutrients containing zinc and selenium, but not vitamins (44
). In another, larger (N=725), randomized, double-blind, placebo-controlled intervention study, low-dose supplementation of zinc and selenium significantly increased the humoral response in institutionalized elderly after vaccination (45
). The number without respiratory tract infections during the study was also found to be higher in elderly that received trace elements over a 2-year period (45
). While these studies suggest a protective effect of zinc against respiratory infections, contribution from other nutrients present in the mixture cannot be ruled out.
The results from our current study, in addition to these earlier findings, suggest that elderly with low serum zinc concentrations might benefit from zinc supplementation. Such a measure has the potential to reduce not only the number of episodes and duration of pneumonia and the total and duration of antibiotic use due to pneumonia, but also overall deaths in the elderly. Randomized, double blind, controlled studies are needed to determine the efficacy of zinc supplementation as a potential low cost intervention to reduce morbidity and mortality due to pneumonia in this vulnerable population.