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Zinc for the common cold.

1. Cochrane Database Syst Rev. 2013 Jun 18;(6):CD001364. doi: 10.1002/14651858.CD001364.pub4. Zinc for the common cold. Singh M(1), Das RR. Author information: (1)Department of Pediatrics, Post Graduate Institute ofMedical Education and Research, Chandigarh, India. meenusingh4@gmail.com Update

Zinc for the common cold.

2. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD001364. doi: 10.1002/14651858.CD001364.pub3. Zinc for the common cold. Singh M(1), Das RR. Author information: (1)Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India, 160012. Update i

Sugar-free zinc gluconate glycine lozenges (Cold-Eeze) do not adversely affect glucose control in patients with type 1 or type 2 diabetes mellitus.

3. Am J Ther. 2001 Jul-Aug;8(4):247-52. doi: 10.1097/00045391-200107000-00007. Sugar-free zinc gluconate glycine lozenges (Cold-Eeze) do not adversely affect glucose control in patients with type 1 or type 2 diabetes mellitus. Schwartz SL(1), Fischer JS, Kipnes MS. Author information: (1)Diabete

The role of zinc lozenges in treatment of the common cold.

4. Ann Pharmacother. 1998 Jan;32(1):63-9. doi: 10.1345/aph.17128. The role of zinc lozenges in treatment of the common cold. Garland ML(1), Hagmeyer KO. Author information: (1)John Cochran Veterans Affairs Medical Center, St. Louis, MO, USA. OBJECTIVE: To summarize and critique the medical liter

WITHDRAWN: Zinc for the common cold.

5. Cochrane Database Syst Rev. 2015 Apr 30;2015(4):CD001364. doi: 10.1002/14651858.CD001364.pub5. WITHDRAWN: Zinc for the common cold. Singh M(1), Das RR. Author information: (1)Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India, 16

WITHDRAWN: Zinc for the common cold.

6. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001364. doi: 10.1002/14651858.CD001364.pub2. WITHDRAWN: Zinc for the common cold. Marshall I. Update in Cochrane Database Syst Rev. 2011 Feb 16;(2):CD001364. doi: 10.1002/14651858.CD001364.pub3. Update of Cochrane Database Syst Rev. 2000

Zinc for the common cold.

7. Cochrane Database Syst Rev. 2000;(2):CD001364. doi: 10.1002/14651858.CD001364. Zinc for the common cold. Marshall I(1). Author information: (1)National Center of Epidemiology and Population Health, Australian National University, Canberra, Australia, 0200. marshali@health.qld.gov.au Update i

Zinc for prevention and treatment of the common cold.

1. Cochrane Database Syst Rev. 2024 May 9;5(5):CD014914. doi: 10.1002/14651858.CD014914.pub2. Zinc for prevention and treatment of the common cold. Nault D(1), Machingo TA(2), Shipper AG(3), Antiporta DA(4), Hamel C(5), Nourouzpour S(6), Konstantinidis M(7)(8), Phillips E(9), Lipski EA(1), Wieland LS(10). Author information: (1)Maryland University of Integrative Health, Laurel, MD, USA. (2)Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA. (3)Health Sciences and Human Services Library, University of Maryland, Baltimore, Baltimore, MD, USA. (4)Department of Epidemiology, Johns Hopkins University, Baltimore, USA. (5)Canadian Association of Radiologists, Ottawa, Canada. (6)Toronto General Hospital, UHN, Toronto, Canada. (7)Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. (8)Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada. (9)Department of Nutritional Sciences, University of Wisconsin - Madison, Madison, Wisconsin, USA. (10)Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. Update of doi: 10.1002/14651858.CD014914. BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold. Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DOI: 10.1002/14651858.CD014914.pub2 PMCID: PMC11078591 PMID: 38719213 [Indexed for MEDLINE] Conflict of interest statement: Daryl Nault: declares no conflict of interest. Taryn Machingo: declares no conflict of interest. Andrea G Shipper: declares no conflict of interest. Daniel A Antiporta: declares no conflict of interest. Candyce Hamel: declares no conflict of interest. Sahar Nourouzpour: declares no conflict of interest. Menelaos Konstantinidis: reports being a Statistical Editor for Cochrane Acute Respiratory Infections, but had no role in the editorial process of this review. Erica Phillips: declares no conflict of interest. Elizabeth Lipski: declares no conflict of interest. L Susan Wieland: reports funding for Cochrane Complementary Medicine from the US National Institutes of Health, National Center for Complementary and Alternative Medicine, R24 AT001293; paid to institution.

Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study.

2. J Allergy Clin Immunol Pract. 2022 Jul;10(7):1889-1902.e9. doi: 10.1016/j.jaip.2022.02.028. Epub 2022 Mar 6. Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study. Bartosik T(1), Jensen SA(2), Afify SM(3), Bianchini R(4), Hufnagl K(4), Hofstetter G(4), Berger M(1), Bastl M(1), Berger U(1), Rivelles E(5), Schmetterer K(5), Eckl-Dorna J(1), Brkic FF(1), Vyskocil E(1), Guethoff S(6), Graessel A(6), Kramer MF(6), Jensen-Jarolim E(7), Roth-Walter F(8). Author information: (1)Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria. (2)Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria; Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria. (3)Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; Laboratory Medicine and Immunology Department, Faculty of Medicine, Menoufia University, Shibin El Kom, Menoufia, Egypt. (4)Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria. (5)Department of Laboratory Medicine, Center of Translational Research, Medical University of Vienna, Vienna, Austria. (6)Bencard Allergie GmbH, Munich, Germany; Allergy Therapeutics Ltd, Worthing, United Kingdom. (7)Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; Biomedical International R+D GmbH, Vienna, Austria. (8)Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria; Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: franziska.roth-walter@meduniwien.ac.at. BACKGROUND: Functional iron deficiency facilitates allergy development and amplifies the symptom burden in people experiencing allergies. Previously we selectively delivered micronutrients to immune cells with β-lactoglobulin as carrier (holoBLG), resulting in immune resilience and allergy prevention. OBJECTIVE: The clinical efficacy of a food for special medical purposes-lozenge containing β-lactoglobulin with iron, polyphenols, retinoic acid, and zinc (holoBLG lozenge) was assessed in allergic women. METHODS: In a randomized, double-blind, placebo-controlled pilot study, grass- and/or birch pollen-allergic women (n = 51) were given holoBLG or placebo lozenges over 6 months. Before and after dietary supplementation, participants were nasally challenged and the blood was analyzed for immune and iron parameters. Daily symptoms, medications, pollen concentrations, and well-being were recorded by an electronic health application. RESULTS: Total nasal symptom score after nasal provocations improved by 42% in the holoBLG group versus 13% in the placebo group. The combined symptom medication score during the birch peak and entire season as well as the entire grass pollen season improved in allergic subjects supplemented with the holoBLG lozenge by 45%, 31%, and 40%, respectively, compared with the placebo arm. Participants ingesting the holoBLG lozenge had improved iron status with increased hematocrit values, decreased red cell distribution width, and higher iron levels in circulating CD14+ cells compared with the placebo group. CONCLUSIONS: Targeted micronutrition with the holoBLG lozenge seemed to be effective in elevating the labile iron levels in immune cells and reducing the symptom burden in allergic women in this pilot study. The underlying allergen-independent mechanism provides evidence that dietary nutritional supplementation of the immune system is one of the ways to combat atopy. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jaip.2022.02.028 PMID: 35263681 [Indexed for MEDLINE]

Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study.

3. Age (Dordr). 2014 Jun;36(3):9656. doi: 10.1007/s11357-014-9656-x. Epub 2014 Apr 26. Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study. Costarelli L(1), Giacconi R, Malavolta M, Basso A, Piacenza F, DeMartiis M, Giannandrea E, Renieri C, Busco F, Galeazzi R, Mocchegiani E. Author information: (1)Translational Center of Research in Nutrition and Ageing, Scientific and Technologic Pole, INRCA, Ancona, Italy. Zinc is a relevant nutritional factor for the whole life of an organism because it affects the inflammatory/immune response and antioxidant activity, leading to a healthy state. Despite its important function, the dietary intake of zinc is inadequate in elderly. Possible interventions include food fortification because it does not require changes in dietary patterns, the cost is low and it can reach a large portion of the elderly population, including very old subjects. Studies evaluating the impact of Zn-fortified foods on functional parameters in elderly, in particular, in very old individuals, are missing. The objective of this study was to evaluate the efficacy of consumption of a zinc-fortified drinking skim milk (Zn-FMilk) for a period of 2 months in comparison to standard non-fortified milk (No-FMilk) on some biochemical parameters, zinc status, inflammatory/immune response and on a key parameter of the T cell-mediated immunity (thymulin hormone) in healthy very old subjects. The treatment with zinc-fortified milk (Zn-FMilk) is a good omen to increase the cell-mediated immunity in very old age represented by thymulin activity and some cytokine (IL-12p70, IFN-γ) release. At clinical level, a good healthy state occurs in 70 % of the subjects with no hospitalization after 1 year of the follow-up in comparison to very old control subjects that did not participate to crossover design. In conclusion, the Zn-FMilk can be considered a good functional food for elderly, including older people. It might be a good replacement to the zinc tablets or lozenges taking into account the attitude of old people to uptake milk as a preferential food. DOI: 10.1007/s11357-014-9656-x PMCID: PMC4082592 PMID: 24771015 [Indexed for MEDLINE]

Estimating quantile treatment effect on the original scale of the outcome variable: a case study of common cold treatments.

4. Trials. 2025 Nov 24;26(1):541. doi: 10.1186/s13063-025-09265-z. Estimating quantile treatment effect on the original scale of the outcome variable: a case study of common cold treatments. Hemilä H(1), Pirinen M(2). Author information: (1)Department of Public Health, University of Helsinki, POB 20, Helsinki, FI-00014, Finland. harri.hemila@helsinki.fi. (2)Department of Public Health, Department of Mathematics and Statistics, and Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. BACKGROUND: Effects of treatments on continuous outcomes are commonly estimated using the mean difference (in units of measurement) or the ratio of means (percentages), each providing a single average effect across the study population. Quantile treatment effect (QTE) analysis is more informative as it estimates the effect of treatment across the whole population. A limitation of the standard QTE is its presentation over control group quantiles, which can hinder interpretability. Presentation of the effect over the measurement units would often be more informative. METHODS: We introduce a method to estimate back-transformed QTE (BQTE), which presents QTEs as a function of the original outcome values in the control group. This approach uses a bootstrap algorithm to estimate both the BQTE curve and its uncertainty. We further derive informative bounds for the average treatment effect at the upper and lower tails of the distribution. The method was applied to 3 datasets on the treatment of the common cold: zinc gluconate lozenges, zinc acetate lozenges, and nasal carrageenan. RESULTS: Across all 3 datasets, BQTE revealed substantial heterogeneity in treatment effects on the units of measurement scale (days). Specifically, shorter colds showed smaller average effects than longer colds, indicating that the assumption of a constant mean difference across the distribution may be inappropriate. In all cases, the relative scale provided a better summary of the BQTE distribution than the mean difference. CONCLUSIONS: The BQTE method enhances the interpretability of QTEs by presenting results on the outcome's original scale. It provides a nuanced understanding of how the average treatment effect varies across the distribution. BQTE is particularly suited for analyzing continuous clinical outcomes such as illness duration or hospital stay and offers a valuable complement to the standard effect size measures in individual-patient data meta-analysis and clinical trial reporting. © 2025. The Author(s). DOI: 10.1186/s13063-025-09265-z PMCID: PMC12645726 PMID: 41286897 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: None.

Shortcomings in the Cochrane review on zinc for the common cold (2024).

5. Front Med (Lausanne). 2024 Oct 16;11:1470004. doi: 10.3389/fmed.2024.1470004. eCollection 2024. Shortcomings in the Cochrane review on zinc for the common cold (2024). Hemilä H(1), Chalker E(2). Author information: (1)Department of Public Health, University of Helsinki, Helsinki, Finland. (2)National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT, Australia. DOI: 10.3389/fmed.2024.1470004 PMCID: PMC11521859 PMID: 39478818 Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Pitfalls in choosing data examples for methodological work: Bayesian approaches to a fixed effects meta-analysis of zinc lozenges for the common cold.

6. Res Synth Methods. 2023 Jan;14(1):3-4. doi: 10.1002/jrsm.1601. Epub 2022 Sep 23. Pitfalls in choosing data examples for methodological work: Bayesian approaches to a fixed effects meta-analysis of zinc lozenges for the common cold. Hemilä H(1), Chalker E(2). Author information: (1)Department of Public Health, University of Helsinki, Helsinki, Finland. (2)Biological Data Science Institute, Australian National University, Canberra, Australia. Comment in Res Synth Methods. 2023 Jan;14(1):2. doi: 10.1002/jrsm.1600. DOI: 10.1002/jrsm.1601 PMID: 36097354 [Indexed for MEDLINE]

Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.

7. JRSM Open. 2017 May 2;8(5):2054270417694291. doi: 10.1177/2054270417694291. eCollection 2017 May. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. Hemilä H(1). Author information: (1)Department of Public Health, University of Helsinki, Helsinki FI-00014, Finland. OBJECTIVE: To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect. DESIGN: Meta-analysis. SETTING: Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method. PARTICIPANTS: Seven randomised trials with 575 participants with naturally acquired common colds. MAIN OUTCOME MEASURE: Duration of the common cold. RESULTS: The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32). CONCLUSIONS: Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further. DOI: 10.1177/2054270417694291 PMCID: PMC5418896 PMID: 28515951

Duration of the common cold and similar continuous outcomes should be analyzed on the relative scale: a case study of two zinc lozenge trials.

8. BMC Med Res Methodol. 2017 May 12;17(1):82. doi: 10.1186/s12874-017-0356-y. Duration of the common cold and similar continuous outcomes should be analyzed on the relative scale: a case study of two zinc lozenge trials. Hemilä H(1). Author information: (1)Department of Public Health, POB 20 University of Helsinki, Tukholmankatu 8 B, FI-00014, Helsinki, Finland. harri.hemila@helsinki.fi. BACKGROUND: The relative scale has been used for decades in analysing binary data in epidemiology. In contrast, there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute, original measurement, scale. The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations; however, similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes. The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale. METHODS: Individual patient data was available for 2 randomized trials on zinc lozenges for the treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0 days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77 days and 25% reduction, in the duration of colds. In both trials, variance in the placebo group was significantly greater than in the zinc lozenge group. The effect estimates were applied to the common cold distributions of the placebo groups, and the resulting distributions were compared with the actual zinc lozenge group distributions. RESULTS: When the absolute effect estimates, 4.0 and 1.77 days, were applied to the placebo group common cold distributions, negative and zero (i.e., impossible) cold durations were predicted, and the high level variance remained. In contrast, when the relative effect estimates, 43 and 25%, were applied, impossible common cold durations were not predicted in the placebo groups, and the cold distributions became similar to those of the zinc lozenge groups. CONCLUSIONS: For some continuous outcomes, such as the duration of illness and the duration of hospital stay, the relative scale leads to a more informative statistical analysis and more effective communication of the study findings. The transformation of continuous data to the relative scale is simple with a spreadsheet program, after which the relative scale data can be analysed using standard meta-analysis software. The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in standard meta-analysis programs. DOI: 10.1186/s12874-017-0356-y PMCID: PMC5427521 PMID: 28494765 [Indexed for MEDLINE]

Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients: An Individual Patient Data Meta-Analysis.

9. Open Forum Infect Dis. 2017 Apr 3;4(2):ofx059. doi: 10.1093/ofid/ofx059. eCollection 2017 Spring. Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients: An Individual Patient Data Meta-Analysis. Hemilä H(1), Fitzgerald JT(2), Petrus EJ(3), Prasad A(4). Author information: (1)Department of Public Health, University of Helsinki, Finland. (2)Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor. (3)Applied Medical Research, Austin, Texas; and. (4)Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. BACKGROUND: A previous meta-analysis of 3 zinc acetate lozenge trials estimated that colds were on average 40% shorter for the zinc groups. However, the duration of colds is a time outcome, and survival analysis may be a more informative approach. The objective of this individual patient data (IPD) meta-analysis was to estimate the effect of zinc acetate lozenges on the rate of recovery from colds. METHODS: We analyzed IPD for 3 randomized placebo-controlled trials in which 80-92 mg/day of elemental zinc were administered as zinc acetate lozenges to 199 common cold patients. We used mixed-effects Cox regression to estimate the effect of zinc. RESULTS: Patients administered zinc lozenges recovered faster by rate ratio 3.1 (95% confidence interval, 2.1-4.7). The effect was not modified by age, sex, race, allergy, smoking, or baseline common cold severity. On the 5th day, 70% of the zinc patients had recovered compared with 27% of the placebo patients. Accordingly, 2.6 times more patients were cured in the zinc group. The difference also corresponds to the number needed to treat of 2.3 on the 5th day. None of the studies observed serious adverse effects of zinc. CONCLUSIONS: The 3-fold increase in the rate of recovery from the common cold is a clinically important effect. The optimal formulation of zinc lozenges and an ideal frequency of their administration should be examined. Given the evidence of efficacy, common cold patients may be instructed to try zinc acetate lozenges within 24 hours of onset of symptoms. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. DOI: 10.1093/ofid/ofx059 PMCID: PMC5410113 PMID: 28480298

Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis.

10. Br J Clin Pharmacol. 2016 Nov;82(5):1393-1398. doi: 10.1111/bcp.13057. Epub 2016 Jul 28. Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis. Hemilä H(1), Petrus EJ(2), Fitzgerald JT(3), Prasad A(4). Author information: (1)Department of Public Health, University of Helsinki, Helsinki, Finland. harri.hemila@helsinki.fi. (2)Applied Medical Research, Austin, Texas. (3)Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, Michigan. (4)Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA. AIMS: The aim of this study was to determine whether the allergy status and other characteristics of common cold patients modify the effects of zinc acetate lozenges. METHODS: We had available individual patient data for three randomized placebo-controlled trials in which zinc acetate lozenges were administered to common cold patients. We used both one stage and two stage meta-analysis to estimate the effects of zinc lozenges. RESULTS: The total number of common cold patients was 199, the majority being females. Eighty percent of them fell into the age range 20-50 years. One third of the patients had allergies. The one stage meta-analysis gave an overall estimate of 2.73 days (95% CI 1.8, 3.3 days) shorter colds by zinc acetate lozenge usage. The two stage meta-analysis gave an estimate of 2.94 days (95% CI 2.1, 3.8 days) reduction in common cold duration. These estimates are to be compared with the 7 day average duration of colds in the three trials. The effect of zinc lozenges was not modified by allergy status, smoking, baseline severity of the common cold, age, gender or ethnic group. CONCLUSION: Since the effects of zinc acetate lozenges were consistent between the compared subgroups, the overall estimates for effect seemed applicable over a wide range of common cold patients. While the optimal composition of zinc lozenges and the best frequency of their administration should be further investigated, given the current evidence of efficacy, common cold patients may be encouraged to try zinc lozenges for treating their colds. © 2016 The British Pharmacological Society. DOI: 10.1111/bcp.13057 PMCID: PMC5061795 PMID: 27378206 [Indexed for MEDLINE]

The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis.

11. BMC Fam Pract. 2015 Feb 25;16:24. doi: 10.1186/s12875-015-0237-6. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis. Hemilä H(1), Chalker E(2). Author information: (1)Department of Public Health, POB 41, University of Helsinki, Mannerheimintie 172, FIN-00014, Helsinki, Finland. harri.hemila@helsinki.fi. (2)University of Sydney, Sydney, Australia. elizabeth.chalker@gmail.com. BACKGROUND: A previous meta-analysis found that high dose zinc acetate lozenges reduced the duration of common colds by 42%, whereas low zinc doses had no effect. Lozenges are dissolved in the pharyngeal region, thus there might be some difference in the effect of zinc lozenges on the duration of respiratory symptoms in the pharyngeal region compared with the nasal region. The objective of this study was to determine whether zinc acetate lozenges have different effects on the duration of common cold symptoms originating from different anatomical regions. METHODS: We analyzed three randomized trials on zinc acetate lozenges for the common cold administering zinc in doses of 80-92 mg/day. All three trials reported the effect of zinc on seven respiratory symptoms, and three systemic symptoms. We pooled the effects of zinc lozenges for each symptom and calculated point estimates and 95% confidence intervals (95% CI). RESULTS: Zinc acetate lozenges shortened the duration of nasal discharge by 34% (95% CI: 17% to 51%), nasal congestion by 37% (15% to 58%), sneezing by 22% (-1% to 45%), scratchy throat by 33% (8% to 59%), sore throat by 18% (-10% to 46%), hoarseness by 43% (3% to 83%), and cough by 46% (28% to 64%). Zinc lozenges shortened the duration of muscle ache by 54% (18% to 89%), but there was no difference in the duration of headache and fever. CONCLUSIONS: The effect of zinc acetate lozenges on cold symptoms may be associated with the local availability of zinc from the lozenges, with the levels being highest in the pharyngeal region. However our findings indicate that the effects of zinc ions are not limited to the pharyngeal region. There is no indication that the effect of zinc lozenges on nasal symptoms is less than the effect on the symptoms of the pharyngeal region, which is more exposed to released zinc ions. Given that the adverse effects of zinc in the three trials were minor, zinc acetate lozenges releasing zinc ions at doses of about 80 mg/day may be a useful treatment for the common cold, started within 24 hours, for a time period of less than two weeks. DOI: 10.1186/s12875-015-0237-6 PMCID: PMC4359576 PMID: 25888289 [Indexed for MEDLINE]

Zinc lozenges may shorten the duration of colds: a systematic review.

12. Open Respir Med J. 2011;5:51-8. doi: 10.2174/1874306401105010051. Epub 2011 Jun 23. Zinc lozenges may shorten the duration of colds: a systematic review. Hemilä H(1). Author information: (1)Department of Public Health, University of Helsinki, Helsinki, Finland. BACKGROUND: A number of controlled trials have examined the effect of zinc lozenges on the common cold but the findings have diverged. The purpose of this study was to examine whether the total daily dose of zinc might explain part of the variation in the results. METHODS: The Medline, Scopus and Cochrane Central Register of Controlled Trials data bases were searched for placebocontrolled trials examining the effect of zinc lozenges on common cold duration. Two methods were used for analysis: the P-values of the trials were combined by using the Fisher method and the results of the trials were pooled by using the inverse-variance method. Both approaches were used for all the identified trials and separately for the low zinc dose and the high zinc dose trials. RESULTS: Thirteen placebo-controlled comparisons have examined the therapeutic effect of zinc lozenges on common cold episodes of natural origin. Five of the trials used a total daily zinc dose of less than 75 mg and uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%). CONCLUSIONS: This study shows strong evidence that the zinc lozenge effect on common cold duration is heterogeneous so that benefit is observed with high doses of zinc but not with low doses. The effects of zinc lozenges should be further studied to determine the optimal lozenge compositions and treatment strategies. DOI: 10.2174/1874306401105010051 PMCID: PMC3136969 PMID: 21769305

Non-antibiotic treatments for upper-respiratory tract infections (common cold).

13. Respir Med. 2005 Dec;99(12):1477-84. doi: 10.1016/j.rmed.2005.09.039. Non-antibiotic treatments for upper-respiratory tract infections (common cold). Arroll B(1). Author information: (1)Department of General Practice and Primary Health Care, University of Auckland, Private Bag 92019, Auckland, New Zealand. b.arroll@auckland.ac.nz OBJECTIVES: To review the seven Cochrane reviews of non-antibiotic treatment for the common cold. METHODS: Each Cochrane review was read and summarized, and results presented as relative risks and, where possible, numbers needed to treat. RESULTS: The main theme that runs through these Cochrane reviews is the variable quality of the primary studies. In general, the reviewers are fairly cautious about the benefits of any of the treatments other than first-dose decongestants and antihistamine-decongestant combinations. For antihistamines alone, the reviewers were clear about the lack of efficacy except in the high-quality studies in which a global improvement in symptoms was noted. Some studies were statistically significant, but the Cochrane reviewers were guarded about how clinically significant they were. For Echinacea, problems were found with the quality of the studies and the wide range of different forms of this substance. Heated humidified air seemed to be effective in the UK and Israel, but not the USA, making definitive statements about efficacy difficult. Over-the-counter medication for cough seemed to have no documented benefit in children under the age of 5 years. Letosteine (a mucolytic) may be effective in children but is not available in the UK. Bisolvon (a mucolytic) was found to be effective for cough in only one study. For older children and adults, dextromethorphan may be effective (two out of three studies showed benefit), and guiafenesin (an expectorant) showed mixed benefit in two trials. Dexbrompheniramine (a sedating antihistamine)/pseudoephedrine (6 mg/120 mg twice daily for 1 week) was significantly more effective than placebo for severity of cough, whereas, in another study, loratadine (a non-sedating antihistamine)/pseudoephedrine (5 mg/120 mg twice daily for 4 days) did not show any difference between the study groups. Vitamin C may have a small role in preventing the common cold, with possibly a greater role in high-intensity physical activity and sub-arctic conditions. Zinc lozenges seemed to be effective, but the issue of unblinding due to taste was a methodological issue of concern to the reviewers. The benefits and harms are calculated as numbers needed to treat for one person to benefit (NNTB) and numbers needed to treat for one person to harm (NNTH), and were calculated by the author. CONCLUSION: Most non-antibiotic treatments for the common cold are probably not effective. The most promising are dextromethorphan, bisolvon and guiaphenesin for cough, antihistamine-decongestant combinations for a wide range of symptoms, nasal decongestants (at least for the first dose) and possibly zinc lozenges. DOI: 10.1016/j.rmed.2005.09.039 PMID: 16291073 [Indexed for MEDLINE]