PMID 38719213 Zinc for prevention and treatment of the common cold Meta-analysis (Cochrane) · Cochrane Database Syst Rev, 2024 34 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s, 8,526 people - zinc does not prevent colds (RR 0.93) but may shorten an ongoing cold (-2.37 days, low certainty).
Key summary
The 2024 CochraneAn international network that rigorously reviews and synthesizes evidence. review pooling 34 studies (15 prevention, 19 treatment) and 8,526 participants. Zinc did not clearly lower the risk of catching a cold (relative risk 0.93, low certainty). When used to treat an existing cold, mean duration may fall (mean difference -2.37 days, low certainty), but variation between trials was very large. Non-serious adverse events rose with treatment (relative risk 1.34, moderate certainty). The conclusion is little or no prevention effect and weak evidence for shortening duration.
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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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 23775705 Zinc for the common cold Meta-analysis (Cochrane) · Cochrane Database Syst Rev, 2013 16 treatment and 2 prevention trials - zinc shortened cold duration by 1.03 days (lozengeA tablet meant to dissolve slowly in the mouth, keeping zinc in contact with the throat and mouth.s ≥75 mg/day), but with bad-taste and nausea side effects.
Key summary
A CochraneAn international network that rigorously reviews and synthesizes evidence. review pooling 16 treatment trials (1,387 participants) and 2 prevention trials (394 participants). Zinc significantly shortened cold duration (mean difference -1.03 days) but not symptom severity, with very high heterogeneity (89%). Adverse events (overall OR 1.58), bad taste (OR 2.31), and nausea (OR 2.15) increased. The authors suggested lozengeA tablet meant to dissolve slowly in the mouth, keeping zinc in contact with the throat and mouth.s at 75 mg a day or more started within 24 hours of onset, while weighing benefit against side effects.
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BACKGROUND: The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results. OBJECTIVES: To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance. SEARCH METHODS: In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47 to 0.88) (P = 0.006) (I(2) statistic = 88%), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.58, 95% CI 1.19 to 2.09) (P = 0.002), bad taste (OR 2.31, 95% CI 1.71 to 3.11) (P < 0.00001) and nausea (OR 2.15, 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. The very high heterogeneity means that the averaged estimates must be viewed with caution. AUTHORS' CONCLUSIONS: Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 27378206 Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis Individual-patient meta-analysis · Br J Clin Pharmacol, 2016 Individual-patient data from 3 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s, 199 people - zinc acetate lozengeA tablet meant to dissolve slowly in the mouth, keeping zinc in contact with the throat and mouth.s shortened colds by about 2.7–2.9 days (vs a 7-day average).
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of individual patient data (199 people) from three randomized placeboAn inert dummy treatment used as the comparison baseline.-controlled trials of zinc acetate lozengeA tablet meant to dissolve slowly in the mouth, keeping zinc in contact with the throat and mouth.s. Lozenge use shortened colds by about 2.7–2.9 days (against a 7-day average), and the effect was consistent regardless of allergy status, smoking, baseline severity, age, or sex. The authors judged that, on current evidence, cold patients may be encouraged to try zinc lozenges.
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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. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 32342851 Zinc Supplementation Reduces Common Cold Duration among Healthy Adults: A Systematic Review of Randomized Controlled Trials with Micronutrients Supplementation Systematic review · Am J Trop Med Hyg, 2020 Review of 20 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s - micronutrients other than vitamin C did not prevent colds, but zinc alone shortened duration by 2.25 days.
Key summary
A systematic review of how single-micronutrient supplementation affects cold incidence and management in healthy adults (20 studies, 10 on zinc). Micronutrients other than vitamin C did not reduce cold incidence or symptom severity. Zinc alone, however, may reduce cold duration by about 2.25 days (95% CI -3.39 to -1.12). The direction is that prevention is hard while shortening duration may be possible.
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The common cold had resulted in significant economic and social burden worldwide. The effect of vitamin C on preventing common cold in healthy adults has been investigated extensively, but not that of other micronutrients. Thus, we aim to assess the effects of providing micronutrients singly through oral means, on cold incidence, and/or management (in terms of cold duration and symptom severity) in healthy adults from systematically searched randomized controlled trials. From four electronic databases, 660 identified studies were screened and data were extracted from 20 studies (zinc, 10; vitamin D, 8; and vitamins A and E, 2). The quality of selected studies was assessed using the Cochrane risk of bias tool and certainty in the outcomes was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. The review found that micronutrients supplementation, except vitamin C, may not prevent cold incidence or reduce symptom severity among healthy adults. However, zinc supplementation was observed to potentially reduce cold duration by 2.25 days (when zinc is provided singly, 95% CI: -3.39, -1.12). This suggests that zinc supplementation may reduce the overall burden due to common cold among healthy adults. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 27996088 Oral zinc for treating diarrhoea in children Meta-analysis (Cochrane) · Cochrane Database Syst Rev, 2016 33 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s, 10,841 children - shortens diarrhea in children over 6 months in deficient settings (WHO-recommended); no effect under 6 months or in well-nourished children.
Key summary
A CochraneAn international network that rigorously reviews and synthesizes evidence. review pooling 33 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s and 10,841 children, most in Asian countries at high risk of zinc deficiency. In children older than six months, acute diarrhea duration was shortened by about half a day (mean difference -11.46 hours) and fewer cases persisted to day seven (relative risk 0.73). In malnourished children the effect was larger, about a full day (high certainty). Under six months there was no effect, and vomiting rose in both age groups. In settings where deficiency and malnutrition are uncommon, no benefit was confirmed.
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BACKGROUND: In developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). OBJECTIVES: To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers. SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS: Both review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using either a fixed-effect or random-effects model) and assessed heterogeneity.We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Thirty-three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency. Acute diarrhoeaThere is currently not enough evidence from well-conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence).In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD -11.46 hours, 95% CI -19.72 to -3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD -26.39 hours, 95% CI -36.54 to -16.23; 419 children, 5 trials, high certainty evidence).Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, 2 trials, moderate certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, moderate certainty evidence).None of the included trials reported serious adverse events. However, zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence). Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, 5 trials, moderate certainty evidence). AUTHORS' CONCLUSIONS: In areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well-nourished children, and in settings where children are at low risk of zinc deficiency. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 11594942 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 RCT · Arch Ophthalmol, 2001 3,640 older adults at high AMD risk - a combination with high-dose zinc (80 mg) lowered progression risk (antioxidants+zinc OR 0.72).
Key summary
An 11-center double-masked trial (AREDS) in 3,640 people aged 55–80 at risk of AMD. A combination of antioxidants plus zinc (80 mg a day, with 2 mg copper) significantly lowered progression to advanced AMD versus placeboAn inert dummy treatment used as the comparison baseline. (odds ratio 0.72, 99% CI 0.52–0.98). Zinc alone was 0.75 (99% CI 0.55–1.03), not statistically clear. The result is confined to a high-risk group that already had substantial AMD, and copper was added to the high-dose zinc to prevent deficiency.
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BACKGROUND: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. OBJECTIVE: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. DESIGN: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. MAIN OUTCOME MEASURES: (1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. RESULTS: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. CONCLUSIONS: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ FDA (openFDA) Zinc sulfate injection - drug label (copper deficiency warning)
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View original ↗ FDA (openFDA) Cold-EEZE (zinc gluconate lozenge) - OTC label (cold duration and drug interactions)
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View original ↗ USDA FoodData Central Chickpeas (garbanzo beans), mature seeds, cooked, boiled, with salt (FDC 173799)
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