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Effects of Zinc Supplementation in Occurrence and Duration of Common Cold in School Aged Children During Cold Season: a Double-Blind Placebo-Controlled Trial

Authors:
Rahim Vakili at Mashhad University of Medical Sciences
Rahim Vakili
Mohammad Vahedian at Mashhad University of Medical Sciences
Mohammad Vahedian
Gholam-Hossian Khodaei
Gholam-Hossian Khodaei
Gholam-Hossian Khodaei
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Mahmoud Mahmoudi at Mashhad University of Medical Sciences
Mahmoud Mahmoudi
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Abstract and Figures

Objective: Zinc deficiency is common in children in developing countries due to low intake of animal foods, and high dietary phytate content. Zinc deficiency impairs overall immune function and resistance to infection. The effect of zinc on the common cold is still questionable. To determine whether supplementation of zinc could reduce frequency rate and duration of common cold during cold season in school aged children living in a low socioeconomic suburb of Mashhad (Altimor), north-east Iran. Methods: We designed a randomized double-blind, placebo-controlled efficacy trial. Subjects were 200 grade 2 primary school children who all completed the trial. Intervention supplementation was zinc sulfate tablets (10 mg elemental) and placebo tablets for case and control groups, respectively. Tablets were taken on a daily basis, 6 days a week, for 5 months (November to March). Findings: Among the zinc-supplemented group common cold incidence of 1.37±0.86 episodes per child during the study period was recorded in comparison to 3.15±0.55 cold episodes per child among the placebo group (P<0.001). Mean overall missing days from school was 0.55±1.09 days and 1.35±1.79 days for zinc-supplemented and placebo groups, respectively. The need for administration of antibiotics for bacterial infections (pharyngitis, acute otitis media, sinusitis, pneumonia) were 20 and 47 courses for zinc-supplemented and placebo groups, respectively (P<0.01). Conclusion: This study showed that zinc supplementation has a beneficial impact on the occurrence of common cold.
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* Corresponding Author;
Address: DepartmentofPublicHealthHealthfacultyMashhadUniversityofMedicalsciences,Mashhad,Iran
E-mail:vahedianm@mums.ac.ir
©2009byPediatricsCenterofExcellence,Children’sMedicalCenter,TehranUniversityofMedicalSciencs, Allrightsreserved.
EffectsofZincSupplementationinOccurrenceandDurationof
CommonColdinSchoolAgedChildrenduringColdSeason:a
DoubleBlindPlaceboControlledTrial
RahimVakili1,MD;MohammadVahedian*2,MCs;GholamHossianKhodaei3,PharmMD;
MahmoudMahmoudi4,MD
1. DepartmentofPediatrics,MashhadUniversityofMedicalSciences,Mashhad,Iran
2. DepartmentofPublicHealth,MashhadUniversityofMedicalSciences,Mashhad,Iran
3. ProvinceHealthCenter,MashhadUniversityofMedicalSciences,Mashhad,Iran
4. ImmunologyResearchCenter,MashhadUniversityofMedicalSciences,Mashhad,Iran
Received:Nov25,2008;FinalRevision:Mar17,2009;Accepted:Aug23,2009
Abstract
Objective:Zinc deficiencyiscommoninchildrenindeveloping countriesduetolowintakeof
animal foods, and high dietary phytate content. Zinc deficiency impairs overall immune
functionandresistancetoinfection.Theeffectofzinconthecommoncoldisstillquestionable.
To determine whether supplementation of zinc could reduce frequency rate and duration of
commoncoldduringcoldseasoninschoolagedchildrenlivinginalowsocioeconomicsuburb
ofMashhad(Altimor),north‐eastIran.
Methods:We designed a randomized double‐blind, placebo‐controlled efficacy trial. Subjects
were200grade2primaryschoolchildrenwhoallcompletedthetrial. Intervention
supplementation was zinc sulfate tablets (10 mg elemental) and placebo tablets for case and
controlgroups,respectively.Tabletsweretakenonadailybasis,6 days a week, for 5 months
(NovembertoMarch).
Findings:Amongthe zinc‐supplemented groupcommoncoldincidenceof 1.37±0.86 episodes
perchildduringthestudyperiod was recorded in comparison to 3.15±0.55 cold episodes per
child among the placebo group (P<0.001). Mean overall missing days from school was
0.55±1.09 days and 1.35±1.79 days for zinc‐supplemented and placebo groups, respectively.
The need for administration of antibiotics for bacterial infections (pharyngitis, acute otitis
media, sinusitis, pneumonia) were 20 and 47 courses for zinc‐supplemented and placebo
groups,respectively(P<0.01).
Conclusion:Thisstudyshowedthatzincsupplementationhasabeneficialimpact on the
occurrenceofcommoncold.
IranianJournalofPediatrics,Volume19(Number4),Dec2009,Pages:376380
KeyWords:ZincSupplementation;Commoncold;UpperrespiratoryInfection;Children
Original Article
Iran J Pediatr
Dec 2009; Vol 19 (No 4), Pp:376-380
www.SID.ir
Archive of SID
377
Iran J Pediatr; Vol 19 (No 4); Dec 2009
Introduction
Zincisanessentialmicronutrientforhuman
growth, development, and immune function.
Mild to moderate zinc deficiency can be best
detectedthroughapositiveresponseto
supplementation trials. Zinc supplementation
hasbeen shown tohave a positiveeffect on the
incidenceofdiarrhea,andpneumonia[1].
Upper respiratory tract viral infections are
one of the most common reasons for physician
visits.Schoolagedchildrenmayexperience6to
8coldsperyear[2].Inchildren,thisillnessisalso
moreextensivethaninadultsandusually
requires medical attention. Statistics indicate
thatmorethan 80% of commoncoldsrequiring
medical attention affect children and
adolescents[3].
Zinc salts have been found to inhibit
rhinovirus replication invitro, possibly by
interferingwithrhinovirusproteincleavage[4].It
has also been suggested that cold symptoms,
sneezingandnasalcongestion,mightbereduced
byelevationsinintranasalzincsalts,producinga
chemicalclamp,ormaybeduetocorrectionofa
subclinicalzincdeficiency[5,6].
Several controlled trials of treatment of
common cold with zinc have been published;
however,there are onlyafewcommunity‐based
longitudinal studies that have been conducted
with zinc supplementation for prevention of
commoncoldduringcoldseason[7].
To investigate the effect of zinc supplemen‐
tation on the prevention of occurrence and the
needforantibioticadministration,weperformed
anintervention trial among school aged Iranian
childreninsuburbofMashhad.
SubjectsandMethods
The study was a randomized, double‐blind,
placebo‐controlled, community‐based inter‐
vention trial conducted between November
2004 and March 2005 in Altimor suburb of
Mashhad,northeastIran.Theprojectwas
approved by the scientific advisory and ethical
committees of Mashhad University of Medical
Sciences.Writteninformedconsentformswere
signed by the parents before including the
children in the study. For ethical reasons and
limitationofcostwedidnotmeasureplasma
Zinklevelsinthisstudy.
A total of 200 children (aged 78 to 120
months) were randomly assigned to daily (6
days in week) supplementation with 10 mg
elementalzincasatablet(n=100,50males, and
50females),orplacebo(n=100,50males,and50
females).
Foreachchildthatwasenrolledinthestudy,a
standardized questionnaire was completed to
obtain family details including basic
demographic and socioepidemiologic data. The
subjects were free of chronic diseases, such as
sickle cell disease, or protein‐energy
malnutrition. All participants were observed on
adaily basis for any medicalsign and symptom
especiallycoldsymptoms.Thisdailysurveillance
for the detection of any sign and symptom of
common cold and other possible diseases was
conductedbytrainedhealthworkers.
These workers were also responsible for
proper administration of the zinc or placebo
tablets. Regular field visits (once a week) for
additionaldata collectionandsupervisionofthe
health workers were made by our physician.
Commoncoldwas defined as thepresence of at
least two of the following symptoms: cough,
headache, hoarseness, muscle ache, nasal
drainage,nasalcongestion,scratchythroat,sore
throat,sneezing,andfever.
Data were analyzed using statistical software
packagesSPSSll.5(SPSS,Inc,Chicago,IL)and
EpiInfo(CenterforDiseaseControland
Prevention,Atlanta, GA) using the χ2 test,t‐test
and ANOVA, P values less than 0.05 was
consideredstatisticallysignificant.
Findings
Table l summarizes the demographic charac‐
teristicsofparticipants.Theaverageoccurrence
ofcommoncoldwas1.73±0.86inzincrecipients
and3.15±0.55inplaceborecipients(P<0.001)
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ZincSupplementationandDurationofCommonCold; R Vakili, et al
Table1:Demographicfindingsof200studentstreatedwithzincsulfateorPlacebo
VariableZincgroupPlacebogroup
Pvalue
Age(month)
Mean(SD*) 93.7(7.38) 93.1(7.35) 0.09
SexMale
Female
50
50
50
50
Numberoffamily
members4.7(2.2) 4.5(2.1) 0.7
SmokerParent18 19 0.1
*SD:StandardDeviation
(Table2).Missingdaysfromschoolduring5
months of study were 0.55±1.09 days (per
student) and 1.35±1.79 days (per student) in
zinc‐supplemented and control groups,
respectively (P<0.001). In the zinc‐
supplemented group, three participants
complained from mild gastrointestinal
discomfortwhichwasresolvedwithinfewdays
andtherewasnoneedfortheirexclusionfrom
thestudy.
Discussion
Millions of people throughout the world may
haveinadequatelevelsofzincintheirdietdueto
limited access to zinc‐rich foods (animal
products,oystersandshellfish)andthe
abundance of zinc inhibitors such as phytate,
commoninplant‐baseddiets[8].
Zinc is a key component of the cell
architectureandisrequiredfortheproduction
ofover200enzymesincludingphosphatase,
metalloproteinases, oxidoreductase, and
transferase which are involved in protein
synthesis,nucleicacid metabolism, and immune
function[18].Zincdeficiency is commonin young
children in the developing countries and is
associated with reduced immuno‐competence
and increased rates of serious infectious
diseases[9].Severalstudieshaveshownthatzinc
supplementation has a positive influence on
linear,motordevelopmentandweightgain[19].
Community‐based studies conducted among
childrenofdifferentage groups have shown the
beneficialimpact of zinc supplementationinthe
form of reduced diarrhea episodes in children
with zinc deficiency, since this supplementation
maylead toacceleratedregeneration ofmucosa,
increased levels of brush border enzymes,
enhancedcellularimmunity,andhigherlevels of
secretoryantibodies[10].
Table2: Mediancommoncoldoccurrenceneedforantibioticmissingschool
Among200StudentsTreatedwithZincsulfateorPlacebo
VariableZincgroupPlacebogroupPvalue
Averagecommoncold
occurrence(SD)
Max
Min
1
.7(0.86)
6
0
3.1(0.55)
8
0
<0.001
Needforantibiotic
administration20 47 <0.001
Daysmissingschool0.55±1.09 1.35±1.79 <0.001
*SD:StandardDeviation
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Iran J Pediatr; Vol 19 (No 4); Dec 2009
Wefoundthatsupplementationwithzincwas
associated with a decrease in the average
occurrence of commoncold duringcold months
of year, among children living in suburbs of
Mashhadwithlowsocioeconomicstatus.Wealso
found that supplementation with zinc was
associated with a decrease in the average
durationandseverityofcommoncold.
Prasad and coworkers showed a beneficial
effectof zinclozenges for reduction of duration
and severity of cold symptoms[7]. They believed
improvement in cold symptoms was related to
the antioxidant anti–inflammatory effect of
zinc[19].
However, previous trials failed to show a
beneficialeffectofzincfortreatmentofcommon
cold, perhaps because inadequate doses or
inappropriate formulations of zinc were used,
resulting in lack of bioavailable zinc[11,12]. Three
other double‐blind placebo‐controlled trials
evaluated the prophylactic and therapeutic
efficacyofzincgluconateglycinelozenges.Inthe
first study involving 57 volunteers,
administrationofzincgluconatelozenge(23mg
every 2 hours for 4.5 days) started one day
before inoculation with human rhinovirus,
reducedthetotalmeanclinicalscoreto5.7from
8.2 with placebo[13,14].Inanotherstudy69
subjectswereinoculatedwithhumanrhinovirus,
andthe12whoexperiencedcoldsymptomwere
randomly allocated to receive either zinc
gluconate lozenges or matched placebo every 2
hoursfor6dayswhileawake.Onceagainzinc
treatment significantly reduced clinical scores
compared to placebo[15]. Retrospective chart
analysis study by McElroy and coworkers
providesstrongsupportforthebeneficialeffects
of zinc in school‐aged subjects with common
cold. They concluded that treatment with zinc
canreducedurationofcoldsigns andsymptoms
and the need for antibiotics, and prophylaxis
maydecreasetheincidenceofcolds
[16]. Hulisz
showedthatzincadministrationwithin24hours
of the onset of common cold may reduce the
duration and severity of symptoms of common
cold[17].According toAmericanFamilyPhysician
guidelinezincisnotrecommendedfortreatment
of common cold because of these inconsistent
studyresults[20].
In our study only 20 participants in zinc
supplementation group required antibiotics for
treatment of upper respiratory tract infection
compared to 47 individuals that needed
antibiotictherapyinplacebogroup.
Recently, Kurugol and coworkers carried out a
prospectivestudytodeterminetheprophylactic
andtherapeuticeffectivenessofzincsulphatefor
the common cold in children. The results of the
study showed that the use of zinc sulphate
significantly reduced the risk of colds andcold‐
relatedschoolabsences[3].
Conclusion
Inconclusionweshowedthatsupplemen‐tation
with zinc was associated with significant
decreaseofthefrequencyofcolds,andreduction
inthedurationandseverityofthesymptomsof
common cold. In addition, the need for use or
misuseofantibioticswasreduced.
Fortification of more commonly used foods
such as bread with zinc salts may be beneficial.
However,furtherinvestigationisrequired.
Acknowledgment
Thisstudy wassupportedbygrantNo. 83047of
vicepresidentforresearch,MashhadUniversity
ofMedicalSciences.Participationofthechildren
andtheirparentsisalsoacknowledged.
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... The search strategy yielded 3928 unique publications once duplicates were removed across databases (Supplementary File S2). Thirty-nine RCT studies (across 43 publications) met eligibility criteria including eight dietary supplement ingredients: echinacea (N = 6; n = 1708 subjects) [14][15][16][17][18][19], elderberry (N = 1; n = 312) [20], garlic (N = 2; n = 266) [21][22][23], vitamin A (N = 2; n = 1719) [24,25], vitamin C (N = 3; n = 237) [26][27][28], vitamin D (N = 18; n = 19,309) [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48], vitamin E (N = 1; n = 652) [49,50] and zinc (N = 6; n = 1445) [51][52][53][54][55][56], involving populations including children, adults and seniors, exposed to stressors described as stressful air travel, intense exercise, academic stress, exposure to winter months, environmental stressors such as poor living environments or where deficiency in certain nutrients is prevalent, and subjects inoculated with a virus. After title and abstract screening, the authors decided to exclude prebiotic and probiotic studies from this current review due to complexities in which these ingredients are categorized/defined in terms of dietary supplements vs. food sources. ...
... Studies of low quality  Studies report statistics in varying ways and selective outcomes reporting of concern  Both studies report on these outcomes as secondary outcomes only  No research in healthy adults meeting eligibility criteria  Risk is associated with very high doses  Vitamin A in multi-ingredient dietary supplements at low amounts appears safe Vitamin C 1000 mg/day taken prophylactically up to 90 days in duration throughout the winter months 3 studies (n = 237) adolescent competitive swimmers (N = 1) [26], adults in the UK (N = 1) [28], males with adequate-low plasma C levels (N = 1) [27] 1 study in males showed up to 45% less risk of developing symptoms RR 0. 55 Three studies show some benefit of taking 1000 mg vitamin C per day throughout the winter months. Study involving males with adequate to low vitamin C levels show less risk of getting sick if taking vitamin C prophylactically during the winter months. ...
... Four studies (n = 1355 participants) included school aged children up to the age of 15 years, living outside of the US who took various forms of zinc for up to seven months, to include the winter months. Children took between 10-20 mg/day of zinc in the forms: zinc bisglycinate-Qualimed, Thailand [53], elemental zinc [55], and zinc sulphate supplied by Berko Ilac Company, Turkey [51] or a Peruvian pharmaceutical Lab (Instituto Quimioterapico, Peru) [54]. According to Kurugol et al. [51] if children experienced symptoms, they were given 30 mg/day for up to 10 days rather than 15 mg/day during the prevention stage. ...
Select Dietary Supplement Ingredients for Preserving and Protecting the Immune System in Healthy Individuals: A Systematic Review
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  • Nov 2022
Immune health products represent approximately 10% of all US dietary supplement sales. Claims made on products to support or boost the immune system are attractive to the otherwise healthy consumer who may or may not be experiencing certain life stressors. The purpose of this systematic review is to critically evaluate the purported benefits and/or potential harms of select dietary supplement ingredients frequently listed on the labels of products having immune health or related market claims. With a focus on resilience, research questions were related to whether dietary supplement ingredients are efficacious in preserving and protecting immune health in healthy individuals; and when faced with a stressor, whether taking a supplement prophylactically can assist in maintaining health and resisting or bouncing back more quickly. Thirty-nine randomized controlled studies involving populations including children, adults and seniors exposed to stressors, such as air travel, intense exercise, academic stress, and/or exposure to winter weather, met eligibility criteria. The studies included eight of the 27 supplement ingredients identified through a market-driven scoping review. Those ingredients used in single ingredient products were echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Whereas some studies may point to evidence for benefit, specific gaps preclude the authors from making firm statements with regard to the overall evidence-base for these products and ingredients and in answering the research questions. As we move toward a vision of health promotion and resilience rather than a sole focus on disease prevention and treatment, further work in this area of dietary supplements is of utmost importance.
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... AURIs can be prevented by practicing physical interventions like regular hand washing, using disposable handkerchiefs, wearing face masks and gargeling 34 . Probiotics (like Lactobacillus spp.), use of herbs and Zinc are also found to be fruitful preventions [35][36][37][38] . ...
Acute Respiratory Infections in Northern Pakistan: An Epidemiological Approach
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... Pre efekt liečby je však nevyhnutná skorá aplikácia, a to už v priebehu prvých 12-24 hodín od začiatku prodromálnych príznakov. Odporúča sa aplikácia zvý šenej dávky, minimálne 75 mg zinku denne u dospelého pacienta po dobu 5 dní [21, [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Použitie zinku v liečbe akútnej rinosinusitídy odporúčajú aj medzinárodné smernice na liečbu akútnej rinosinusitídy -European Position Paper on Rhinosinusitis [38,39]. ...
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Zinok má komplexné imunomodulačné, protivírusové, protizápalové a cytoprotektívne účinky, preto patrí medzi efektívne spôsoby liečby a prevencie respiračných vírusových infekcií. Lekárnik je zdravotnícky pracovník, ktorý najčastejšie a ako prvý rieši samoliečbu rôznych respiračných infekcií. Tie sú takmer vždy spôsobené vírusmi. Článok opisuje úlohu zinku pre správne fungovanie imunitného systému, vrátane mechanizmov jeho protivírusového pôsobenia. Lekárnik môže odporúčať zinok v liečbe akútnych infekcií horných dýchacích ciest (napr. prechladnutie), alebo ako doplnkovú liečbu a prevenciu iných respiračných infekcií či chronických respiračných ochorení s predpokladom deficiencie zinku. V článku sa tiež uvádza možné využitie zinku ako súčasti liečby a prevencie ochorenia covid-19. Kľúčové slová zinok – respiračné infekcie – protivírusový účinok – lekárnik Zinc has complex immunomodulatory, antiviral, anti-inflammatory and cytoprotective effects, making it an effective way of treating and preventing respiratory viral infections. Pharmacists are the first-line healthcare professionals frequently handling self-treatment of various respiratory infections, which are almost always caused by viruses. The article describes zinc’s role in the immune system being able to function correctly, including its antiviral mechanisms of action. A pharmacist may recommend zinc to treat acute upper respiratory tract infections, such as the common cold, or as adjunctive therapy, and to prevent other respiratory infections or chronic respiratory diseases with a presumption of zinc deficiency. The article also discusses the possible use of zinc as part of treatment and prevention of covid-19. Key words zinc – respiratory infections – antiviral effect – pharmacist
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... Clinical studies using zinc supplementation are primarily limited to rhinovirus infection, and are often grouped with other "common cold" viruses such as influenza and coronaviruses with several studies using zinc lozenges and formulations. The replication of rhinoviruses was potently inhibited by Zinc salts in in vitro experiments and amelioration of clinical symptoms associated with common cold has been reported to occur following increased level of zinc salts in the nasal cavity (Vakili et al., 2009). For instance, the administration of zinc bisglycinate reduced significantly the duration of illness and manifestation of symptoms under experimental conditions (Sanguansak & Lakkana, 2013). ...
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Article
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the etiological agent for the Coronavirus Disease 2019 (COVID‐19). The COVID‐19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID‐19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID‐19 with varying degrees of successes. Zinc possesses potential health benefits against COVID‐19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID‐19 pandemic. Practical applications The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the etiological agent for the Coronavirus Disease 2019 (COVID‐19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID‐19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti‐inflammatory actions have become alternative to stem the tide of COVID‐19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID‐19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID‐19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines.
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... This agreed with the study by Rahim et al. [22] who suggested that zinc through its antioxidant effect may improve symptoms of respiratory tract infection. ...
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... This agreed with the study by Rahim et al. [22] who suggested that zinc through its antioxidant effect may improve symptoms of respiratory tract infection. ...
Serum zinc levels in hospitalized children with pneumonia: a hospital-based case–control study
Article
Full-text available
  • Dec 2019
Abstract Background Zinc is an important micronutrient in humans. Globally, pneumonia represents 18% of mortality in children under 5 years of age and the main infectious purpose of early life mortality. There is a higher pneumonia risk in a population with zinc deficiency. The aim of our study is to compare the level of serum zinc in children with pneumonia with age, sex, and nutritional matched healthy controls. Patients and methods Serum zinc level in 90 children admitted with pneumonia was compared with the matched controls. Results The mean level of serum zinc in children with pneumonia (67.5±21.8) is significantly lower than that of controls (91.8±19.94) with (P
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Zinc for prevention and treatment of the common cold
Article
  • May 2024
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.
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Reduzieren Vitamin C, Vitamin D und Zink die Prävalenz und die Schwere viraler Atemwegsinfekte?
Article
  • Feb 2024
Die Rolle von Mikronährstoffen wie Vitamin C, Vitamin D oder Zink in der Prävention und Therapie von Erkältungskrankheiten wird seit Langem diskutiert. Die Evidenzlage hierzu ist gemischt, was der Heterogenität der Studienpopulationen, dem oftmals fehlenden Erregernachweis sowie der unterschiedlichen Dauer, Frequenz und Dosis der Mikronährstoffgabe geschuldet ist. Festgehalten werden kann, dass es sinnvoll ist, die Supplementation individuell an den Ernährungsstatus, an Grunderkrankungen und Laborparameter anzupassen. Ein Vitamin-D-Mangel sollte ausgeglichen werden. Von einer Vitamin-C-Supplementation profitieren insbesondere Personen, die unter hohem körperlichen Stress stehen, sowie jene mit Exposition gegenüber Menschen mit akuten Atemwegsinfektionen.
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Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years
Article
Full-text available
  • Mar 2023
Background: Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed. Objectives: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years. Search methods: A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies. Selection criteria: Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. Data collection and analysis: Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events. Main results: We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc. Authors' conclusions: Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high.
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Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta‐analysis
Article
Full-text available
It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID‐19. In this systematic review and meta‐analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS‐CoV‐2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta‐carotene, zinc, iron and long‐chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty‐three studies were included in the meta‐analyses, which was performed for children and adults separately. By stratifying the meta‐analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7–0.96, I² = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79–0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68–0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post‐hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.
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Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory infection in Australian adults
Article
Full-text available
  • Sep 1987
Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individuals in 34 families, 63 (33 zinc and 30 placebo) were considered evaluable, in that the volunteer used the medication at least four times daily for at least 3 days, the average utilization being 5.4 days at an average dose of six lozenges daily. Six users of zinc reported nausea (versus no placebo users), and eight reported an unpleasant taste or aftertaste (versus one placebo user). No benefit was observed among the users of zinc acetate. The mean duration of symptoms in users of the zinc was 12.1 days, compared with 7.7 days in those who used the placebo. Nor was any beneficial effect of zinc evident among the four zinc-treated versus the two placebo-treated individuals from whom rhinovirus was grown.
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Inhibition by zinc of rhinovirus protein cleavage: Interaction of zinc with capsid polypeptides
Article
  • May 1976
Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.
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Zinc Deficiency: A Public Health Problem?
Article
  • Sep 1991
  • Am J Dis Child
• Zinc deficiency occurs in individuals and populations whose diets are low in sources of readily bioavailable zinc such as red meat, and high in unrefined cereals that are rich in phytate and dietary fibers. Dietary zinc deficiency was described nearly three decades ago among the poor of the Middle East. It is now known to occur in children and adolescents from widely diverse areas including Egypt, Iran, Turkey, China, Yugoslavia, Canada, and the United States; and among pregnant women from Iran, Turkey, the United Kingdom, Australia, and the United States. Major manifestations include retarded growth and development and an increased incidence of pregnancy complications. Other manifestations may include suppressed immunity, poor healing, dermatitis, and impairments in neuropsychological functions. Precise information as to the numbers of people affected by dietary zinc deficiency is not available. Even so the nature of diets associated with zinc deficiency suggests that mild deficiency is common in some populations. (AJDC. 1991;145:853-859)
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Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges
Article
  • Jan 1988
Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10² tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10² TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo. There were also statistically significant reductions in the mean total nasal secretion weights and total tissue counts. Zinc, however, had no significant effect on the rate or amount of virus excreted by volunteers. We conclude that zinc gluconate lozenges are reasonably well tolerated and that they have a significant effect on the signs and symptoms of colds caused by rhinoviruses, although the mechanism of action remains obscure.
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Is zinc deficiency a public problem?
Article
  • Jan 1995
  • NUTRITION
Zinc is essential for all species. Human zinc deficiency related to diet was recognized 30 yr ago among adolescents in Iran and Egypt. Subsequent factorial calculations, balance studies, and tracer studies of bioavailability and turnover established the amounts of zinc needed for equilibrium and dietary factors that impair retention. Comparison of dietary intakes of zinc with requirements suggested many women and children are at risk of deficiency. Epidemiological studies associated low plasma levels of zinc with abnormal pregnancy outcomes and controlled intervention trials showed that zinc repletion improved pregnancy outcomes. Low iron nutriture, a common phenomenon in women, was shown to be associated with low zinc nutriture. Thus the hypothesis that zinc deficiency is a public health problem appears to be true.
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How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action
Article
  • Apr 1996
  • MED HYPOTHESES
Clinical studies have shown that ionic zinc (Zn2+) dissolved in the mouth shortened manifestations of the common cold significantly, by an unknown mechanism. The observed immediate effect on symptoms is consonant with osmotic transport of Zn2+, placing a temporary chemical clamp on critical nerves. It is proposed that transient elevation of Zn2+ concentration in and around the nasal cavity facilitates Zn2+ complexation with known intercellular adhesion molecule binding sites on rhinovirus surfaces which prevents rhinovirus binding to cells and interrupts infection. The crystallographically determined surface of rhinovirus-14 has been found to contain binding sites for at least 360 Zn2+. Such binding of Zn2+ would be stabilized by numerous histidine, methionine, tyrosine and carboxyl/carboxylate groups known to line the HRV-14 surface canyons. The resulting blockage of HRV docking with intercellular adhesion molecule binding sites is proposed to be responsible for the observed reduction of the duration of colds by statistically significant and clinically meaningful times.
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Zinc and Diarrhea in Infants
Article
  • Jul 1997
  • J TRACE ELEM MED BIO
Due to dietary modifications including the intake of cereals, vegetables and the frequent use of soy milk instead of breast milk, children in developing countries with diarrhea frequently suffer from zinc deficiency. Furthermore, diarrhea leads to excess zinc losses. Beside low energy intake zinc deficiency contributes to continued diarrhea, which in turn accounts for half of the deaths from diarrhea in children. Zinc supplementation leads to accelerated regeneration of the mucosa, increased levels of brush-border enzymes, enhanced cellular immunity and higher levels of secretory antibodies. In addition, in stunted children zinc supplementation results in enhanced catch-up growth via higher levels of insulin-like growth factor-I. Growth retardation is closely related to the risk of diarrheal diseases in children. These pathophysiological conclusions are supported by several controlled clinical traits which have provided evidence that zinc supplementation results in significant reduction in the risk of continued diarrhea. However, it remains to be clarified whether these benefits are attributable to pharmacological effects or if they can be related to the correction of an underlying deficiency state.
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