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Advances in Nutrition (Bethesda, Md.) Jul 2019Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types,... (Review)
Review
Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections.
Topics: Antiviral Agents; Dietary Supplements; Humans; Immunity, Humoral; Immunity, Innate; Virus Diseases; Zinc
PubMed: 31305906
DOI: 10.1093/advances/nmz013 -
Advances in Food and Nutrition Research 2021Since the discovery of manifest Zn deficiency in 1961, the increasing number of studies demonstrated the association between altered Zn status and multiple diseases. In... (Review)
Review
Since the discovery of manifest Zn deficiency in 1961, the increasing number of studies demonstrated the association between altered Zn status and multiple diseases. In this chapter, we provide a review of the most recent advances on the role of Zn in health and disease (2010-20), with a special focus on the role of Zn in neurodegenerative and neurodevelopmental disorders, diabetes and obesity, male and female reproduction, as well as COVID-19. In parallel with the revealed tight association between ASD risk and severity and Zn status, the particular mechanisms linking Zn and ASD pathogenesis like modulation of synaptic plasticity through ProSAP/Shank scaffold, neurotransmitter metabolism, and gut microbiota, have been elucidated. The increasing body of data indicate the potential involvement of Zn metabolism in neurodegeneration. Systemic Zn levels in Alzheimer's and Parkinson's disease were found to be reduced, whereas its sequestration in brain may result in modulation of amyloid β and α-synuclein processing with subsequent toxic effects. Zn was shown to possess adipotropic effects through the role of zinc transporters, zinc finger proteins, and Zn-α2-glycoprotein in adipose tissue physiology, underlying its particular role in pathogenesis of obesity and diabetes mellitus type 2. Recent findings also contribute to further understanding of the role of Zn2+ in spermatogenesis and sperm functioning, as well as oocyte development and fertilization. Finally, Zn was shown to be the potential adjuvant therapy in management of novel coronavirus infection (COVID-19), underlining the perspectives of zinc in management of old and new threats.
Topics: Alzheimer Disease; Animals; Autism Spectrum Disorder; COVID-19; Diabetes Mellitus, Type 2; Female; Humans; Male; Neurodegenerative Diseases; Neurodevelopmental Disorders; Nutritional Status; Obesity; Parkinson Disease; Reproduction; Zinc; COVID-19 Drug Treatment
PubMed: 34112355
DOI: 10.1016/bs.afnr.2021.01.003 -
European Journal of Medical Research May 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a pneumonia outbreak and was called 2019 novel coronavirus disease (COVID-19). COVID-19... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a pneumonia outbreak and was called 2019 novel coronavirus disease (COVID-19). COVID-19 emerged in December 2019 and now considered a pandemic. Zinc supplementation can reduce mortality in patients with severe pneumonia. This study aimed at meta-analysis of the results of related studies and evaluate the effect of zinc supplementation on COVID-19 mortality.
METHODS
A systematic search has conducted for manuscripts through PUBMED/Medline and Google Scholar (Cochrane guideline has considered it as the gray literature) up to September 2021. This meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guideline for evaluation of the effect zinc supplementation on COVID-19 mortality. Based on the heterogeneity a fixed-effect or random-effect model, the OR and 95% CI were used to assess the combined risk.
RESULTS
After assessment, five studies with 1506 participants in case and control groups were included in meta-analysis. The OR for one study was not estimable, and the pool OR was estimated for other studies with 1398 participants. The meta-analysis showed that zinc supplementation in cases led to a significant lower risk of mortality when it was compared with the control group; pooled OR (95% CI) was 0.57 [0.43, 0.77] (P < 0.001).
CONCLUSION
This meta-analysis has suggested that zinc supplementation is associated with a lower mortality rate in COVID-19 patients. Zinc supplementation could be considered as a simple way and cost benefit approach for reduction of mortality in COVID-19 patients.
Topics: COVID-19; Dietary Supplements; Humans; Pandemics; SARS-CoV-2; Zinc
PubMed: 35599332
DOI: 10.1186/s40001-022-00694-z -
Nutrients Sep 2019The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild... (Review)
Review
The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.
Topics: Antineoplastic Agents; Antioxidants; Diet; Humans; Immune System; Neoplasms; Zinc
PubMed: 31546724
DOI: 10.3390/nu11102273 -
Molecules (Basel, Switzerland) Sep 2020In this study, we critically review the literature concerning the relation of Mg, Fe, Zn, Cu and Se and attention-deficit/hyperactivity disorder (ADHD). Elemental status... (Review)
Review
In this study, we critically review the literature concerning the relation of Mg, Fe, Zn, Cu and Se and attention-deficit/hyperactivity disorder (ADHD). Elemental status is estimated using peripheral blood parameters, hair, urine, daily intake and response to supplementation. The observed associations between concentration levels of the elements Mg, Fe, Zn, Cu and Se and ADHD symptoms are contradictory. This is partly due to the heterogeneity and complexity of the disorder. As a trend, lower ferritin and zinc levels can be observed. However, this correlation is not causative, as illustrated by placebo-controlled trials reporting conflicting evidence on the efficacy of supplementation. Well-defined studies on changes in concentration levels of the elements in relation to ADHD symptoms before and after treatment with therapeutics it will be possible to shed more light on the significance of these elements in this behavioral disorder. The discussion on whether a change in concentration of an element is cause or consequence of ADHD is not within the scope of this article.
Topics: Attention Deficit Disorder with Hyperactivity; Copper; Humans; Iron; Magnesium; Selenium; Zinc
PubMed: 32992575
DOI: 10.3390/molecules25194440 -
JAMA Jan 2020Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.
OBJECTIVE
To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.
DESIGN, SETTING, AND PARTICIPANTS
The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.
INTERVENTIONS
Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.
RESULTS
Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).
CONCLUSIONS AND RELEVANCE
Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01857310.
Topics: Adolescent; Adult; DNA Fragmentation; Dietary Supplements; Female; Fertilization in Vitro; Folic Acid; Humans; Infertility, Male; Live Birth; Male; Middle Aged; Semen; Semen Analysis; Sperm Count; Treatment Failure; Young Adult; Zinc
PubMed: 31910279
DOI: 10.1001/jama.2019.18714 -
International Journal of Molecular... Oct 2020Several studies proposed the importance of zinc ion in male fertility. Here, we describe the properties, roles and cellular mechanisms of action of Zn in spermatozoa,... (Review)
Review
Several studies proposed the importance of zinc ion in male fertility. Here, we describe the properties, roles and cellular mechanisms of action of Zn in spermatozoa, focusing on its involvement in sperm motility, capacitation and acrosomal exocytosis, three functions that are crucial for successful fertilization. The impact of zinc supplementation on assisted fertilization techniques is also described. The impact of zinc on sperm motility has been investigated in many vertebrate and invertebrate species. It has been reported that Zn in human seminal plasma decreases sperm motility and that Zn removal enhances motility. Reduction in the intracellular concentration of Zn during epididymal transit allows the development of progressive motility and the subsequent hyper activated motility during sperm capacitation. Extracellular Zn affects intracellular signaling pathways through its interaction with the Zn sensing receptor (ZnR), also named GPR39. This receptor was found in the sperm tail and the acrosome, suggesting the possible involvement of Zn in sperm motility and acrosomal exocytosis. Our studies showed that Zn stimulates bovine sperm acrosomal exocytosis, as well as human sperm hyper-activated motility, were both mediated by GPR39. Zn binds and activates GPR39, which activates the trans-membrane-adenylyl-cyclase (tmAC) to catalyze cAMP production. The NHE (Na/H-exchanger) is activated by cAMP, leading in increased pHi and activation of the sperm-specific Ca channel CatSper, resulting in an increase in [Ca], which, together with HCO, activates the soluble adenylyl-cyclase (sAC). The increase in [cAMP] activates protein kinase A (PKA), followed by activation of the Src-epidermal growth factor receptor-Pphospholipase C (Src-EGFR-PLC) cascade, resulting in inositol-triphosphate (IP) production, which mobilizes Ca from the acrosome, causing a further increase in [Ca] and the development of hyper-activated motility. PKA also activates phospholipase D1 (PLD1), leading to F-actin formation during capacitation. Prior to the acrosomal exocytosis, PLC induces phosphadidylinositol-4,5-bisphosphate (PIP) hydrolysis, leading to the release of the actin-severing protein gelsolin to the cytosol, which is activated by Ca, resulting in F-actin breakdown and the occurrence of acrosomal exocytosis.
Topics: Acrosome; Animals; Fertility; Humans; Male; Reproductive Techniques, Assisted; Sperm Capacitation; Sperm Motility; Spermatozoa; Zinc
PubMed: 33096823
DOI: 10.3390/ijms21207796 -
The New England Journal of Medicine Sep 2020The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting.
METHODS
We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration.
RESULTS
The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration.
CONCLUSIONS
Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).
Topics: Antidiarrheals; Child, Preschool; Diarrhea; Diarrhea, Infantile; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Male; Medication Adherence; Vomiting; Zinc
PubMed: 32966722
DOI: 10.1056/NEJMoa1915905 -
Nutrients Aug 2020Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological...
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Topics: Adult; Dietary Supplements; Dysmenorrhea; Endometriosis; Female; Humans; Insulin Resistance; Lipid Metabolism; Male; Menstrual Cycle; Polycystic Ovary Syndrome; Pregnancy; Reproduction; Zinc
PubMed: 32824334
DOI: 10.3390/nu12082464 -
Nutrients Nov 2021Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder common from childhood to adulthood, affecting 5% to 12% among the general population in...
UNLABELLED
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder common from childhood to adulthood, affecting 5% to 12% among the general population in developed countries. Potential etiological factors have been identified, including genetic causes, environmental elements and epigenetic components. Nutrition is currently considered an influencing factor, and several studies have explored the contribution of restriction and dietary supplements in ADHD treatments. Iron is an essential cofactor required for a number of functions, such as transport of oxygen, immune function, cellular respiration, neurotransmitter metabolism (dopamine production), and DNA synthesis. Zinc is also an essential trace element, required for cellular functions related to the metabolism of neurotransmitters, melatonin, and prostaglandins. Epidemiological studies have found that iron and zinc deficiencies are common nutritional deficits worldwide, with important roles on neurologic functions (poor memory, inattentiveness, and impulsiveness), finicky appetite, and mood changes (sadness and irritability). Altered levels of iron and zinc have been related with the aggravation and progression of ADHD.
OBJECTIVE
This is a systematic review focused on the contribution of iron and zinc in the progression of ADHD among children and adolescents, and how therapies including these elements are tolerated along with its effectiveness (according to PRISMA guidelines).
METHOD
The scientific literature was screened for randomized controlled trials published between January 2000 to July 2021. The databases consulted were Medline, PsycINFO, Web of Science, and Google Scholar. Two independent reviewers screened studies, extracted data, and assessed quality and risk of bias (CONSORT, NICE, and Cochrane checklists used).
CONCLUSION
Nine studies met the eligibility criteria and were selected. Evidence was obtained regarding the contribution of iron-zinc supplementation in the treatment of ADHD among young individuals. The discussion was focused on how the deficits of these elements contribute to affectation on multiple ADHD correlates, and potential mechanisms explaining the mediational pathways. Evidence also suggested that treating ADHD with diet interventions might be particularly useful for specific subgroups of children and adolescents, but further investigations of the effects of these diet interventions are needed.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Dietary Supplements; Ferrous Compounds; Humans; Randomized Controlled Trials as Topic; Zinc
PubMed: 34836314
DOI: 10.3390/nu13114059