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Cited by 516Trace Elements in HealthIron Metabolism and DisordersExercise and Physiological Responses

Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress

Open access
Prasad, Ananda S, Beck, Frances WJ, Bao, Bin, Fitzgerald, James T, Snell, Diane C, Steinberg, Joel D, Cardozo, Lavoisier J·2007·The American Journal of Clinical Nutrition
DOI 10.1093/ajcn/85.3.837
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Abstract

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.

AI snapshot

Written from the paper’s full text.

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).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/ajcn/85.3.837

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 67 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In zinc-supplemented elderly, 17 subjects had no evidence of any infection during study, versus 3 in placebo.

    “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.”
    Quote in the paperSubstantial claim
  • Findingown data

    Ex vivo generation of TNF-α increased significantly over 12 months in placebo elderly.

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data

    Baseline IL-10 generation by Th2 cells was significantly higher in healthy elderly than in younger adults.

    “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.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In zinc-supplemented elderly, total incidence of infections over 12 months was 7, versus 35 in placebo.

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data

    Zinc supplementation for 12 months significantly reduced mean incidence of infections per subject compared with placebo in healthy elderly.

    “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).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 22
  • May combine two claims. 11

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Plasma NO concentration was nonsignificantly lower in zinc-supplemented than placebo elderly at 6 months.

    “A nonsignificantly lower concentration of NO was observed in the zinc group at the end of 6 mo.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Ex vivo generation of IL-10 decreased nonsignificantly with time in zinc-supplemented elderly.

    “Ex vivo generation of IL-10 decreased nonsignificantly with time in the zinc group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    At baseline, generated IL-10 concentration was higher in the zinc group than in the placebo group (P=0.015).

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Persons caring for patients, drawing blood, or running laboratory analyses were blinded to treatment assignment.

    “The persons caring for the patient, involved in drawing blood, or running laboratory analyses were blinded to the assignment.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Elderly subjects were randomly assigned in pairs to zinc or placebo using envelopes.

    “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).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study planned 50 participants to have about 80% power to detect a halving of infection incidence, assuming SD 0.95 and two-sided P=0.05.

    “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%.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The nurse practitioner who evaluated subjects for infections was blinded to treatment assignment.

    “The nurse-practitioner was blinded to the treatment assignment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Reports indicate that older adults experience zinc deficiency and increased infection susceptibility from impaired cell-mediated immunity.

    “Zinc deficiency and susceptibility to infections due to cell-mediated immune dysfunction have been reported to occur in the elderly (3,4).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Cakman, 1997, Zinc supplementation reconstitutes the production of interferon-α by leukocytes from elderly persons, J Interferon Cytokine Res source

      Not checked in the free run.

    • cites [4] Prasad, 1993

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In the RT-PCR substudy, baseline plasma zinc was similar in the zinc and placebo arms (86.38 vs 88 μg/dL, P=0.35).

    “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).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All subjects provided written informed consent.

    “All subjects provided written informed consent.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Age, sex, and ethnicity were balanced at baseline across the zinc and placebo arms.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Trials of TNF neutralization in septic shock and of IL-1 receptor antagonist or TNF antibody in rheumatoid arthritis imply these cytokines matter in those diseases.

    “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.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [13] Beutler, 1995, TNF, Immunity and inflammatory disease: lessons of the past decade, J Invest Med

      Not checked in the free run.

    • cites [14] Pennington, 1993, Therapy with antibody to tumor necrosis factor in sepsis, Clin Infect Dis source

      Not checked in the free run.

    • cites [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 in the free run.

    • cites [16] Opal, 2002, Impact of basic research on tomorrow's medicine: anti-inflammatory cytokines, Chest source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Wayne State University's Human Investigation Committee approved the protocol, which followed the 1983 revision of the Helsinki Declaration.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chronic inflammation has been linked to elevated cardiovascular death rates among older adults.

    “In addition, chronic inflammatory processes have been implicated in high cardiovascular mortality in elderly subjects (11,12).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Ward, 1995, Cytokines, inflammation, and autoimmune diseases, Hosp Pract source

      Not checked in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxidative stress contributes importantly to several age-related chronic diseases, including atherosclerosis, cancer, neurodegeneration, and immune disorders.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Castro, 2001, Reactive oxygen species in human health and disease, Nutrition source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Infection diagnosis followed the long-term care facility practice guidelines for fever and infection evaluation.

    “the practice guidelines for evaluation of fever and infections in long-term care facilities was used as our basis (26).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Bentley, 2000, Practice guideline for evaluation of fever and infection in long-term care facilities, Clin Infect Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The senior-center participants were in better health than elderly nursing-home residents.

    “Thus, the subjects from St Patrick's were healthier than elderly persons living in nursing homes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Labcatal Laboratories verified and certified the capsules' zinc content.

    “The zinc content of capsules was checked and certified by Labcatal Laboratories.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Higher TNF-α and IL-1β have been linked to cutaneous leishmaniasis, and more lipid peroxidation products have been linked to zinc deficiency in children with chronic giardiasis.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [18] Demirci, 2003, Serum iron, zinc and copper levels and lipid peroxidation in children with chronic giardiasis, J Health Pop Nutr

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NF-κB is involved in gene expression of TNF-α and IL-1β in human monocytes and macrophages and HL-60 cells, and the effect of zinc in inhibiting gene expression of TNF-α and IL-1β is cell specific.

    “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).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [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 in the free run.

    • cites [21] Prasad, 2001, Zinc activates NF-κB in HUT-78 cells, J Lab Clin Med source

      Not checked in the free run.

    • cites [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 in the free run.

    • cites [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 in the free run.

    • cites [24] Jaattela, 1996, A20 zinc finger protein inhibits TNF and IL-1 signaling, J Immunol source

      Not checked in the free run.

    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In HL-60 cells, zinc increases expression of A20 and binding of A20 transactivating factor to DNA, resulting in inhibition of induced NF-κB activation.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Prasad, 2004, Anti-oxidant effect of zinc in humans, Free Rad Biol Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Providing zinc to zinc-deficient subjects should improve host defense and increase resistance to pathogens by enhancing the immune response.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The current study provides a link between zinc supplementation, increased IL-2 mRNA production, decreased incidence of infections, decreased generation of inflammatory cytokines, and decreased oxidative stress in elderly subjects.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Low thymulin activity and low IL-2 production have been reported in zinc-deficient elderly subjects.

    “Low thymulin activity and low IL-2 production have been reported in zinc-deficient elderly subjects (36).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Prasad, 2002, Zinc, infection and immune function

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Zinc has several key roles relating to cell signaling, cell activation, gene expression, protein synthesis, and apoptosis.

    “Zinc has several key roles relating to cell signaling, cell activation, gene expression, protein synthesis, and apoptosis (36).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Prasad, 2002, Zinc, infection and immune function

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other investigators have observed that zinc supplementation to elderly subjects increased numbers of circulating T cells in association with improved delayed-type hypersensitivity reactions and immunoglobulin G antibody responses to tetanus toxoid.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Duchateau, 1981, Beneficial effects of oral zinc supplementation on the immune response of old people Am J Med

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The decrease in IL-10 production may increase IL-2 production.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Opal, 1998, Interleukin-10 potential benefits and possible risks in clinical infectious diseases, Clin Infect Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The increase in TNF-α in the placebo group may be an effect of increasing age.

    “We also observed in the placebo group that TNF-␣ increased with time, which suggests that this increase may be an effect of increasing age.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A long-term, still ongoing trial has been conducted for the past 10 years in patients with age-related macular degeneration who received 80 mg elemental zinc as oxide and 2 mg Cu to prevent copper deficiency.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The number of subjects in the trial was small.

    “The limitation of the current study is that the number of subjects in the trial was small.”
    Quote in the paperNot a substantial claim
30 of 30

  • 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.”
5 of 5

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?

  • Zinc supplementation in elderly adults significantly reduces incidence of infection.

    “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]

  • The authors' studies showed that zinc deficiency may affect nearly 30%-40% of well-off healthy ambulatory elderly subjects in the Detroit area, who had decreased plasma zinc and increased plasma lipid peroxidation products and endothelial cell adhesion molecules compared with healthy zinc-sufficient younger adults.

    “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 12-month trial, oxidative stress biomarkers in plasma decreased significantly in the zinc group compared with placebo.

    “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]

  • Zinc deficiency and susceptibility to infections due to cell-mediated immune dysfunction have been reported to occur in the elderly.

    “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 authors' comparison, elderly subjects had lower plasma zinc and higher percentages of cells producing IL-1β and TNF-α and higher generated cytokines than younger subjects.

    “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]

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

    Major

    The 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.

  • White participant counts differ between groups

    Minor

    The 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.

  • E-selectin sample exceeds the reported study cohort

    Minor

    Table 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.

  • IL-2 interaction has conflicting P values

    Minor

    The results give P = 0.0001 for the IL-2 mRNA group-by-time interaction, but Table 7 gives P = 0.001 for that interaction.

  • Baseline zinc values disagree for the separate cohort

    Minor

    For 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.

5 of 5

Cites

Flagged first, then by citations

3 of the 48 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Castle, 1993, Lowering the temperature criterion improves detection of infections in nursing home residents, Aging Immunol Infect Dis, 4, 67
  2. Beck, 1997, Changes in cytokines production and T cell subpopulations in experimentally induced zinc deficient humans, Am J Physiol, E1002

Cited by

Sorted by citations

Related

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
ORCID
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)
DOI
10.1093/ajcn/85.3.837
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
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 › Rehabilitation › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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