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Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress
Open accessAbstract
Background Zinc deficiency, cell-mediated immune dysfunction, susceptibility to infections, and increased oxidative stress have been observed in elderly subjects (ie, those >55 y old). Zinc is an effective antiinflammatory and antioxidant agent.Objectives The primary objective was to determine the effect of zinc on the incidence of total infections in healthy elderly subjects. The secondary objective was to determine the effect of zinc on cytokines and oxidative stress markers.Design A randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in elderly subjects. Fifty healthy subjects of both sexes aged 55-87 y and inclusive of all ethnic groups were recruited for this study from a senior center. The zinc-supplemented group received zinc gluconate (45 mg elemental Zn/d) orally for 12 mo. Incidence of infections during the supplementation period was documented. The generation of inflammatory cytokines, T helper 1 and T helper 2 cytokines, and oxidative stress markers and the plasma concentrations of zinc were measured at baseline and after supplementation.Results Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules. The incidence of infections and ex vivo generation of tumor necrosis factor alpha and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group. Plasma zinc and phytohemagglutin-induced interleukin 2 mRNA in isolated mononuclear cells were significantly higher in the zinc-supplemented than in the placebo group.Conclusions After zinc supplementation, the incidence of infections was significantly lower, plasma zinc was significantly higher, and generation of tumor necrosis factor alpha and oxidative stress markers was significantly lower in the zinc-supplemented than in the placebo group.
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TL;DR
In a 12-month randomized, double-blind, placebo-controlled trial, daily zinc gluconate (45 mg elemental zinc) lowered infection incidence and reduced ex vivo TNF-α and plasma oxidative stress markers in healthy older adults. Zinc also raised plasma zinc and PHA-induced IL-2 mRNA in zinc-deficient elderly participants.
Key findings
- Infection incidence over 12 months was lower with zinc than placebo: 0.29 ± 0.46 vs 1.4 ± 0.95 infections per subject (P < 0.01; effect size 1.46); 29% vs 88% of subjects affected (P = 0.001), and 17 zinc recipients vs 3 placebo recipients had no infection.
- Plasma zinc rose in the zinc group (92.9 ± 9.45 to 104 ± 16.69 µg/dL at 12 mo) while the placebo group trended down (95.7 ± 13.09 to 88.5 ± 9.66; P = 0.0002).
- Ex vivo TNF-α generation fell significantly in the zinc group and rose in the placebo group, with maximal reduction at 6 mo; oxidative stress markers also improved: MDA+HAE 1.66 ± 0.34 to 1.35 ± 0.18 vs 1.70 ± 0.30 to 1.71 ± 0.35 µmol/L (P = 0.0002), and 8-OHdG 0.63 ± 0.16 to 0.50 ± 0.14 vs 0.66 ± 0.13 to 0.68 ± 0.13 ng/mL (P = 0.030).
- In a separate 6-month substudy of zinc-deficient elderly, PHA-induced IL-2 mRNA increased with zinc (0.38 ± 0.07 to 0.63 ± 0.03) but not placebo (0.40 ± 0.05 to 0.39 ± 0.04; P = 0.001); plasma zinc also increased (84.0 ± 3.03 to 97.6 ± 5.98 vs 86.8 ± 2.04 to 89.2 ± 3.06 µg/dL; P = 0.0088).
Methods
- Randomized, double-blind, placebo-controlled 12-month trial in 50 healthy elderly adults aged 55–87 recruited from a senior center; one zinc-group participant dropped out on day 2, leaving complete data for 49 (tables report 24 zinc, 25 placebo). The zinc group received 45 mg elemental zinc/d as zinc gluconate; the primary endpoint was infection incidence, with secondary cytokine and oxidative stress measures.
- Baseline comparisons were made with 31 younger adults aged 18–54 for plasma zinc, adhesion molecules, nitric oxide, MDA, and ex vivo inflammatory cytokines.
- A separate substudy randomized 12 zinc-deficient elderly subjects to zinc or placebo for 6 months to measure plasma zinc and PHA-stimulated IL-2 mRNA by RT-PCR in mononuclear cells; analyses used t tests, Wilcoxon rank-sum, chi-square/Fisher exact, paired t tests, and multivariate repeated-measures models.
Limitations
- The authors state that the trial’s main limitation was its small number of subjects and call for larger zinc trials in the elderly.
- Evident from the text: the IL-2 mRNA substudy had only 6 subjects per group, and oxidative stress markers were measured at 6 months but not repeated at 12 months.
- Evident from the text: participants came from one senior center and were described as healthier than nursing-home residents, which may limit generalizability; some baseline imbalances were noted (higher IL-10 in the zinc group; lower plasma zinc in the zinc substudy group despite randomization).
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seventeen subjects in the zinc-supplemented group had no evidence of any infection during the study, but only 3 subjects in the placebo group had no evidence of infection.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
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In the paper
“Also with time (12 mo of supplementation), the ex vivo generation of TNF-␣ decreased significantly in the zincsupplemented subjects and increased significantly in the placebo group (Table 5).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules.”
- Also stated in: § RESULTS · plain
“IL-10 generated by Th2 cells, which are known to produce a negative effect on IL-2 generated by Th1 cells) was significantly higher in the elderly.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Abstract
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the zinc-supplemented group, the total incidence of infections was 7 (2 from January through March, 0 from April through June, 3 from July through September, and 2 from October through December).In the placebo group, the total incidence of infections was 35 (8 from January through March, 11 from April through June, 7 from July through September, and 9 from October through December).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incidence of infections and ex vivo generation of tumor necrosis factor ␣ and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group.”
- Also stated in: § RESULTS · plain
“The mean incidence of infections per subject in 12 mo was significantly (P 0.01) lower in the zinc-supplemented group (0.29 Ȁ 0.46) than in the placebo group (1.4 Ȁ 0.95; effect size: 1.46).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Their mean plasma zinc concentration at baseline was 94.5 Ȁ 2.54 g/dL, whereas that in the 12 zinc-deficient subjects was 85.4 Ȁ 2.54 g/dL (P ҃ 0.0001).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Reverse transcriptase-polymerase chain reaction for interleukin 2 mRNA
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules.”
- Also stated in: § RESULTS · plain
“Intercellular adhesion molecules, vascular endothelial cell adhesion molecules, and E-selectin in the plasma also were significantly higher in the elderly.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Abstract
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The changes in concentrations of plasma molecular markers of oxidative stress (MDA ѿ HAE and 8-oHdG) between baseline and at the end of 6 mo of zinc supplementation showed a greater (and significant) decrease in the zinc-supplemented group than in the placebo group (Table 6).”
- Also stated in: § Abstract · plain
“The incidence of infections and ex vivo generation of tumor necrosis factor ␣ and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules.”
- Also stated in: § RESULTS · plain
“Plasma zinc was lower and the percentage of cells producing IL-1 and TNF-␣ and the generated concentrations of these cytokines were significantly higher in the elderly subjects.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At baseline, the IL-2 mRNA of the zinc-sufficient subjects was 0.59 Ȁ 0.05 and that of the zinc-deficient subjects was 0.39 Ȁ 0.06 (P ҃ 0.0001).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Reverse transcriptase-polymerase chain reaction for interleukin 2 mRNA
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 22
- It may state two separate claims as one. 11
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A nonsignificantly lower concentration of NO was observed in the zinc group at the end of 6 mo.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ex vivo generation of IL-10 decreased nonsignificantly with time in the zinc group.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The generated IL-10 concentration was, however, higher in the zinc group than in the placebo group (P ҃ 0.015) at baseline, the explanation for which is unclear.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The persons caring for the patient, involved in drawing blood, or running laboratory analyses were blinded to the assignment.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Intervention
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Elderly subjects were randomly assigned in pairs to the zincsupplemented or the placebo group with the use of envelopes that each contained 2 smaller envelopes (1 assigning a subject to zinc treatment and 1 assigning a subject to placebo).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Intervention
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We chose a sample size of 50 for the current study so that we could detect a 50% reduction in the incidence of infections in the zinc-supplemented group, with a SD of 0.95, a 2-sided P value of 0.05, and an approximate power of ͧ80%.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Preliminary study
Strength:plain· not yet calibratedn = 50Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The nurse-practitioner was blinded to the treatment assignment.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Outcome measures
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None of the sources cited for this claim have been checked yet.
In the paper
“Zinc deficiency and susceptibility to infections due to cell-mediated immune dysfunction have been reported to occur in the elderly (3,4).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [3] Cakman, 1997, Zinc supplementation reconstitutes the production of interferon-α by leukocytes from elderly persons, J Interferon Cytokine Res source
- Not checked yetcites [4] Prasad, 1993
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean plasma zinc concentrations at baseline in the zinc and placebo groups were 86.38 Ȁ 3.6 and 88 Ȁ 0.82 g/dL, respectively (P ҃ 0.35).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Reverse transcriptase-polymerase chain reaction for interleukin 2 mRNA
Strength:plain· not yet calibratedn = 12Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“All subjects provided written informed consent.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Subjects
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In the paper
“Neither the ages of the 2 groups or the number of men and women participating in each group differed significantly.An equal number of African Americans and whites participated in the 2 groups.No other variables differed significantly between the groups.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > RESULTS
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In the paper
“TNF neutralization in the treatment of septic shock (13,14) and the use of IL-1 receptor antagonist (IL-1ra) and TNF antibody in the treatment of rheumatoid arthritis (15,16) suggest that these cytokines are important in the pathogenesis of the above disorders.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [13] Beutler, 1995, TNF, Immunity and inflammatory disease: lessons of the past decade, J Invest Med
- Not checked yetcites [14] Pennington, 1993, Therapy with antibody to tumor necrosis factor in sepsis, Clin Infect Dis source
- Not checked yetcites [15] Elliott, 1994, Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor α (CA2) versus placebo in rheumatoid arthritis, Lancet source
- Not checked yetcites [16] Opal, 2002, Impact of basic research on tomorrow's medicine: anti-inflammatory cytokines, Chest source
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study protocol was approved by the Human Investigation Committee of Wayne State University and was in accord with the Helsinki Declaration as revised in 1983.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Subjects
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, chronic inflammatory processes have been implicated in high cardiovascular mortality in elderly subjects (11,12).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [11] Ward, 1995, Cytokines, inflammation, and autoimmune diseases, Hosp Pract source
- Not checked yetcites [12] Kunsch, 2004, Selective inhibition of endothelial and moncyte redox-sensitive genes by AG1–1067: a novel antioxidant and anti inflammatory agent, J Pharm Exp Ther source
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In the paper
“Oxidative stress has been recognized as an important contributing factor in several chronic diseases attributed to aging, such as atherosclerosis and related cardiovascular disorders, mutagenesis and cancer, neurodegeneration, and immunologic disorders and even in the aging process itself (5).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [5] Castro, 2001, Reactive oxygen species in human health and disease, Nutrition source
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In the paper
“the practice guidelines for evaluation of fever and infections in long-term care facilities was used as our basis (26).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Outcome measures
What the sources say
- Not checked yetcites [26] Bentley, 2000, Practice guideline for evaluation of fever and infection in long-term care facilities, Clin Infect Dis source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the subjects from St Patrick's were healthier than elderly persons living in nursing homes.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > Elderly subjects
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The zinc content of capsules was checked and certified by Labcatal Laboratories.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > FIGURE 1.
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None of the sources cited for this claim have been checked yet.
In the paper
“Increases in inflammatory cytokines TNF-␣ and IL-1 have been associated with cutaneous leishmaniasis (17), and increases in lipid peroxidation products were associated with zinc deficiency in children with chronic giardiasis (18).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [17] Kocyigit, 2002, Associations among plasma selenium, zinc, copper, and iron concentrations and immunoregulatory cytokine levels in patients with cutaneous leishmaniasis, Biol Trace Elem Res source
- Not checked yetcites [18] Demirci, 2003, Serum iron, zinc and copper levels and lipid peroxidation in children with chronic giardiasis, J Health Pop Nutr
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nuclear factor-B is involved in the gene expression of TNF-␣ and IL-1 in monocytes and macrophages in humans and HL-60 cells, and the effect of zinc in inhibiting the gene expression of TNF-␣ and IL-1 is cell specific (20 -25).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [20] Prasad, 2002, Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-κB activation, J Lab Clin Med source
- Not checked yetcites [21] Prasad, 2001, Zinc activates NF-κB in HUT-78 cells, J Lab Clin Med source
- Not checked yetcites [22] Krikos, 1992, Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by κB elements, J Biol Chem source
- Not checked yetcites [23] Heyninck, 1999, The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-κB activation at the level of TRAF6, FEBS Lett source
- Not checked yetcites [24] Jaattela, 1996, A20 zinc finger protein inhibits TNF and IL-1 signaling, J Immunol source
- Not checked yetcites [25] Song, 1996, The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-κB activation, Proc Natl Acad Sci U S A source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“We previously provided evidence that, in the promyelocytic leukemia cell line HL-60, which differentiates to the monocyte and macrophage phenotype in response to phorbol-12-myristate-13-acetate, zinc increases the expression of A20 and the binding of A20 transactivating factor to DNA, which results in the inhibition of induced nuclear factor-B activation (19).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > INTRODUCTION
What the sources say
- Not checked yetcites [19] Prasad, 2004, Anti-oxidant effect of zinc in humans, Free Rad Biol Med source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the enhancing effect on the immune response of providing zinc should translate into improved host defense and increased resistance to pathogens in zinc-deficient subjects.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the current study provides an important link between zinc supplementation, increased IL-2 mRNA production, decreased incidence of infections, decreased generation of inflammatory cytokines, and decreased oxidative stress in the elderly subjects.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Low thymulin activity and low IL-2 production have been reported in zinc-deficient elderly subjects (36).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
What the sources say
- Not checked yetcites [36] Prasad, 2002, Zinc, infection and immune function
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Zinc has several key roles relating to cell signaling, cell activation, gene expression, protein synthesis, and apoptosis (36).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
What the sources say
- Not checked yetcites [36] Prasad, 2002, Zinc, infection and immune function
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Other investigators have observed that zinc supplementation to elderly subjects increased the numbers of circulating T cells in association with improved delayed-type hypersensitivity reactions and immunoglobulin G antibody responses to tetanus toxoid (38).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
What the sources say
- Not checked yetcites [38] Duchateau, 1981, Beneficial effects of oral zinc supplementation on the immune response of old people Am J Med
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“We have also observed a decrease in IL-10 production in zinc-supplemented elderly subjects, and this decrease may also have an effect of increasing IL-2 production (40).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
What the sources say
- Not checked yetcites [40] Opal, 1998, Interleukin-10 potential benefits and possible risks in clinical infectious diseases, Clin Infect Dis source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also observed in the placebo group that TNF-␣ increased with time, which suggests that this increase may be an effect of increasing age.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A long-term, still ongoing trial has been conducted for the past 10 y in patients with age-related macular degeneration who received 80 mg elemental zinc as oxide and 2 mg Cu to prevent copper deficiency (41).”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
What the sources say
- Not checked yetcites [41] 2001, A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss: AREDS Report No. 8, Arch Ophthalmol source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The limitation of the current study is that the number of subjects in the trial was small.”
§ Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress 1-3 > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Before this study, zinc had not been reported for managing oxidative stress in elderly people.
“The use of zinc in the management of oxidative stress in the elderly has not, however, been reported.”
The paper relies on this without support.
The elderly participants in the study are representative of the general elderly population.
“Our study showed that zinc supplementation administered to the elderly population resulted in a significant decrease in the incidence of infection.”
The paper relies on this without support.
Ex vivo IL-2 mRNA expression in mononuclear cells reflects in vivo IL-2 production.
“We conclude that zinc is involved in increasing IL-2 production in zinc-deficient elderly subjects by increasing the gene expression of IL-2.”
The paper relies on this without support.
Inflammatory cytokines generate oxidative stress.
“These inflammatory cytokines, in turn, are known to generate oxidative stress.”
The paper relies on this without support.
The plasma zinc criteria used by the authors validly classify elderly subjects as zinc-deficient.
“According to our plasma zinc criteria, Ȃ35% of the elderly subjects in the current study were considered zinc-deficient.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In elderly adults, zinc supplementation significantly reduces the incidence of infection [194].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [194]
In the citing paper
“Our studies also showed that zinc deficiency may affect nearly 30%–40% of the well-off healthy ambulatory elderly subjects in the Detroit area (75, 76). In these subjects, decreased plasma zinc and increased plasma lipid peroxidation products and endothelial cell adhesion molecules compared with the healthy zinc-sufficient younger adults were observed.”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [76]
In the citing paper
“Oxidative stress biomarkers in the plasma also decreased significantly in the zinc group compared with the placebo group (76).”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [76]
In the citing paper
“Zinc deficiency and susceptibility to infections due to cell-mediated immune dysfunction have been reported to occur in the elderly (75, 76).”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [76]
In the citing paper
“A comparison of the baseline data between the younger subjects (ages 18–54, n = 31) and the elderly subjects showed that the plasma zinc was lower and the percentage of cells producing IL-1β and TNF-α and the generated cytokines were significantly higher in the elderly subjects (76).”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [76]
In the citing paper
“The plasma zinc increased, and ex vivo generation of TNF-α and IL-10 decreased significantly in the zinc group compared with the placebo group (76).”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [76]
In the citing paper
“It is estimated that 30-40% of elderly subjects in the Detroit, Michigan, area have mild to moderate zinc deficiency (7).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Baseline zinc comparison is called both significant and nonsignificant
MajorThe results say baseline plasma zinc did not differ significantly between the separate study's groups, whereas the Table 7 note calls the difference significant at P = 0.016.
“At baseline, the plasma zinc and IL-2 mRNA concentrations did not differ significantly between the zinc and placebo group subjects (Table 7).”
“Despite the random assignment of zinc-deficient subjects into zinc or placebo group, the plasma zinc concentration was significantly lower in the zinc group than in the placebo group (P ҃ 0.016).”
White participant counts differ between groups
MinorThe text says the two groups had equal numbers of white participants, but Table 1 lists 17 in the zinc group and 19 in the placebo group.
“An equal number of African Americans and whites participated in the 2 groups.”
“| White | 17 | 19 |”
E-selectin sample exceeds the reported study cohort
MinorTable 2 lists 69 older subjects for the E-selectin measurement, although the study reports complete data on only 49 participants. The text does not account for the additional subjects in that comparison.
“| Plasma E-selectin (ng/mL) | 32.2 Ȁ 13.1 (19) | 84.6 Ȁ 47.6 (69) | 0.001 |”
“One participant in the zinc group dropped out on day 2. We therefore had complete data on 49 participants.”
IL-2 interaction has conflicting P values
MinorThe results give P = 0.0001 for the IL-2 mRNA group-by-time interaction, but Table 7 gives P = 0.001 for that interaction.
“Group ҂ time interactions were significant for IL-2 mRNA (P ҃ 0.0001) and plasma zinc (P ҃ 0.0088) concentrations.”
“| Zinc group | 0.38 Ȁ 0.07 4 | 0.63 Ȁ 0.03 | 0.001 |”
Baseline zinc values disagree for the separate cohort
MinorFor the six-person groups in the separate study, the narrative reports baseline plasma zinc means of 86.38 and 88, while Table 7 reports 84.0 and 86.8.
“The mean plasma zinc concentrations at baseline in the zinc and placebo groups were 86.38 Ȁ 3.6 and 88 Ȁ 0.82 g/dL, respectively (P ҃ 0.35).”
“| Zinc group | 84.0 Ȁ 3.03 | 97.6 Ȁ 5.98 | 0.0088 | | Placebo group | 86.8 Ȁ 2.04 | 89.2 Ȁ 3.06 | |”
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Metadata
- Authors
- Prasad, A. S., Beck, F. W., Bao, B., Fitzgerald, J. T., Snell, D. C., Steinberg, J. D., & Cardozo, L. J.
- Affiliations
- Wayne State University (US)
- Corresponding author
- Prasad, Ananda S
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 85
- Issue
- 3
- Pages
- 837-844
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W1925247835
- Semantic Scholar
- 11116558de00f3cc34601cbec8e847680dbab8ce
- Cited by
- 516
- References
- 48
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 30 · 2023: 24 · 2022: 42 · 2021: 58 · 2020: 50 · 2019: 24 · 2018: 24 · 2017: 28 · 2016: 14 · 2015: 22 · 2014: 31 · 2013: 25 · 2012: 25
- FWCI
- 20.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (5 R01 A150698-04)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- zinc supplementation, zinc deficiency, older adults, infection incidence, cytokines, oxidative stress, TNF-α, IL-10, interleukin-2, T helper cells, plasma zinc, endothelial adhesion molecules, zinc gluconate, immune function
- MeSH terms
- Adolescent, Adult, Aged, Double-Blind Method, Female, Humans, Infections, Male, Middle Aged, Zinc, Incidence, Cytokines, Oxidative Stress, Th1 Cells, Th2 Cells, Dietary Supplements
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