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Title: Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly:A randomized double-blind placebo-controlled trial

Author
item BARNETT, JUNAIDAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DAO, MARIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HAMER, DAVIDSON - Boston University
item KANDEL, RUTH - Hebrew Rehabilation Center For Aged
item BRANDEIS, GARY - Boston University
item WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DALLAL, GERARD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SCHREIBER, ROBERT - Hebrew Rehabilation Center For Aged
item KONG, EUNHEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, SIMIN NIKBIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/2015
Publication Date: 1/27/2016
Citation: Barnett, J., Dao, M.C., Hamer, D.H., Kandel, R., Brandeis, G., Wu, D., Dallal, G.E., Jacques, P.F., Schreiber, R., Kong, E., Meydani, S. 2016. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly:A randomized double-blind placebo-controlled trial. American Journal of Clinical Nutrition. 103(3):942-951. doi: 10.3945/ajcn.115.115188.

Interpretive Summary: The mineral zinc is essential for proper function of the immune system. Generally, the elderly have been shown to have low zinc levels. Additionally, as we age, the function of a specific cell of the immune system the T cell declines. In a previous publication, we showed that 30% of nursing home elderly have low serum zinc levels. Further, those with low serum zinc level had significantly higher occurrence and longer duration of pneumonia as well as all-cause mortality compared to elderly with adequate zinc levels. Thus, the combined issue of aging and zinc deficiency may increase the elderly’s risk for infectious disease. A human study was conducted to explore the effect of zinc supplementation on immune responses in nursing home elderly aged 65 and older over a period of 3 months. The outcome demonstrated an increase in zinc levels in the bloodstream over a 3 month period in those whose blood zinc levels were low. However, those whose zinc levels in the bloodstream were very low did not show an increase in serum level that is considered adequate. Additionally, zinc supplementation significantly increased the number of T cells and their function as measured by their ability to proliferate and increase their numbers. A positive relationship between changes in blood zinc levels and function of T cells was observed. These findings demonstrate that 30 milligrams per day of zinc is capable to correct low serum zinc levels in a majority of nursing home residents with low serum zinc level but not all. A higher level or longer supplementation period might be needed to correct serum zinc levels in those who have very low serum zinc. This correction of zinc deficiency improves the immune response and thus may help prevent infectious diseases in older adults who are at high risk for pneumonia.

Technical Abstract: Background: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve serum zinc concentrations and immunity of nursing home elderly with low serum zinc concentration. Objective: We aimed to determine the effect of supplementation with 30 mg per day of zinc for 3 months on serum zinc concentrations of zinc-deficient nursing home elderly. Design: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged 65or older) who met eligibility criteria, 58 percent had low serum zinc concentration (serum zinc less than 70 micrograms per dL); these 31 were randomized into zinc (30mg zinc per day) (N equals 16) or placebo (5mg zinc per day) (N equals 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored supplementation effects on immune response. Results: Baseline characteristics were similar in the two groups. The difference in the mean change in serum zinc was significantly higher by 16% in the zinc versus placebo group (p equals 0.007), controlling for baseline zinc concentrations. Controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with serum zinc less than or equal to 60 micrograms per dL failed to increase their serum zinc to greater than or equal to 70 micrograms per dL. Zinc supplementation also significantly increased anti-CD3/CD28 and PHA-stimulated T-cell proliferation, and the number of peripheral T cells (p equals 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in number of T cells. Conclusion: Zinc supplementation at 30 mg per day for 3 months is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc level was associated with enhancement of T cell function mainly due to increase in number of T cells.