Immunomodulatory and clinical responses to zinc gluconate supplementation in patients with Behçet's disease: A double-blind, randomized placebo-controlled clinical trial.

BACKGROUND & AIMS: Toll-like receptor (TLR) 2 and 4 are involved in the pathogenesis of Behçet's disease (BD). The current study aimed to investigate the effect of zinc supplementation on TLR-2/4 expression and the clinical manifestations of BD. METHODS: In this double-blind placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day) or placebo groups for 12 weeks. Before and after the intervention, the surface and mRNA expression level of TLR-2 and TLR-4 in the leukocytes, serum level of zinc and tumor necrosis factor-α (TNF-α), quality of life, anthropometric measures, and blood pressure of patients were collected. BD activity was studied using the nonocular Iranian Behçet's disease dynamic activity measure (IBDDAM), Behçet's disease current activity form (BDCAF), and total inflammatory activity index (TIAI) at the pre-and post-intervention phases. The effect sizes were compared between two groups using analysis of covariance. RESULTS: There were significant decrease in TLR-2 mRNA (P = 0.038) and protein expression (P = 0.034) and nonocular IBDDAM score (P = 0.046) in the zinc group compared to placebo at the endpoint. The serum level of zinc was increased in the zinc group (P < 0.001). Zinc supplementation significantly decreased the TLR-4 surface (P = 0.012) and mRNA expression (P = 0.028) within the group. However, this decrease was not significant compared to the placebo group. There was no significant difference between the two groups regarding the serum level of TNF-α, BDCAF, TIAI, quality of life, anthropometric measures, and blood pressure (P > 0.05). CONCLUSIONS: The present study revealed that zinc supplementation significantly improved nonocular IBDDAM score and TLR-2 expression in BD patients. GOV REGISTRATION NUMBER: NCT05098678.

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial.

Importance: There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progression. Objective: To examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. Design, Setting, and Participants: This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Intervention: Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. Outcomes: The primary end point was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. Results: A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. Conclusions and Relevance: In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care. Trial Registration: ClinicalTrials.gov Identifier: NCT04342728.

A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

OBJECTIVE: Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS: In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS: Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS: Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Findings on the effects of zinc supplementation on the lipid profile in patients with type 2 diabetes mellitus (T2DM) are conflicting. The current comprehensive systematic review and meta-analysis aimed to summarize available evidence in this regard. METHODS AND RESULTS: After a systematic search in the online databases, we included the randomized controlled trials (RCTs) investigating the effect of zinc supplementation on lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)] in patients with T2DM. Altogether, 9 studies with a total sample size of 424 patients with T2DM were included in the analysis. Combining 9 effect sizes from 9 RCTs, we found a significant lowering effect of zinc supplementation on serum levels of TG (weighted mean difference (WMD): -17.08, 95% CI: -30.59, -3.58 mg/dL, P = 0.01) and TC (WMD: -26.16, 95% CI: -49.69, -2.62 mg/dL, P = 0.02). Although the overall effect of zinc supplementation on LDL-C levels was not significant, a beneficial effect was seen in studies that administered <100 mg/d zinc. Based on the non-linear dose-response analysis, a greater reduction in serum levels of TC and LDL-C following zinc supplementation was seen at <12 weeks' duration of intervention. Unlike the overall effect size, we found a significant increasing effect of zinc supplementation on serum HDL-C concentrations in most subgroups of RCTs according to the subgroup analyses. CONCLUSION: We found that zinc supplementation may beneficially influence lipid profile in patients with T2DM.

Zinc gluconate supplementation impacts the clinical improvement in patients with ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease that affects the mucous membrane of the colon. The pathogenesis is not clear, but there is evidence of a complex interaction between genetic, environmental, and immunological factors. In this regard, we highlight the role of zinc in the immune system and probable control of the disease. This study evaluated the effect of zinc supplementation on the inflammatory response in patients with ulcerative colitis. A blind interventional study involving 41 patients of both sexes, who underwent either zinc gluconate supplementation (n = 23), or treatment with a placebo (corn starch) (n = 18). Patients were evaluated for dietary zinc intake, plasma and erythrocyte zinc concentrations, and serum levels of Th1/Th2/Th17 type cytokines at baseline (T0) and 30 (T1) and 60 (T2) days after intervention. Patients in the zinc supplementation group had a lower probability of having an adequate zinc intake than placebo. In this same group, there was a significant difference between plasma zinc concentrations (T1 in relation to T0, T2 in relation to T1, and T2 in relation to T0) and erythrocyte zinc (T1 in relation to T0 and T2 in relation to T1). Zinc supplementation resulted in significant changes in the concentrations of IL-2 and IL-10 without differences in the other interleukins. Zinc gluconate intervention in patients with ulcerative colitis improves the nutritional status of this mineral in these patients and positively influences their clinical outcome, reinforcing the role of zinc as an important dietary component in disease control.

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

OBJECTIVE: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection. METHODS: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. RESULTS: Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). CONCLUSIONS: In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities.

The Effect of Zinc Gluconate Supplementation on Symptoms and Tongue Epithelium Regeneration in Non-psoriatic Patients with Migratory Glossitis.

The aim of this study was to evaluate zinc gluconate as a treatment option in patients with symptomatic migratory glossitis (MG). Using simple random sampling, 28 non-psoriatic patients with symptomatic MG were divided into a test and control group. The test group took 20 mg/day of chelated zinc gluconate for one month, and was put on a diet rich in zinc. The control group was only put on a diet rich in zinc. Changes in the size of red atrophied areas (width and length) and the intensity of symptoms were evaluated as primary and secondary outcomes, respectively, at baseline, after therapy, and one month later. In the test group, the mean value of the red atrophy area width and length displayed some significant reduction as a primary outcome. There were no significant changes in the size of red patches in the control group. Secondary outcome showed that the intensity of subjective symptoms in the test group significantly decreased (P=0.042) compared with controls. The filiform papillae had partially or completely regenerated in 85.7% of cases in the test group and in 23.1% of the controls (P=0.001). Red patches with raised keratotic rims may have healed spontaneously and reappeared in constantly changing patterns that are typical for MG. This phenomenon was not observed in patients supplemented with zinc, and new atrophy areas occurred in only one case. Low-dose zinc gluconate.

Atividade in vitro do extrato etanólico de própolis e do digluconato de clorexidina sobre as espécies de Candida isoladas da mucosa bucal de pacientes internados em Unidade de Terapia Intensiva (UTI) / In vitro activity of ethanolic extract of propolis and chlorhexidine digluconate on Candida species isolated from the oral mucosa of patients hospitalized in the Intensive Care Unit (ICU)

Avaliou-se a atividade dos extratos de própolis e digluconato de clorexidina em Candida sp isoladas da mucosa bucal de pacientes em UTI. Foram determinadas as concentrações fungicidas mínimas (CFM) e comparadas, nas doses sub-inibitórias, à produção de exoenzimas proteinase e fosfolipase e formação de franjas. Em 72 isolados foram avaliadas a atividade antifúngica pela técnica de microdiluição em série, na “base 2”, a produção das exoenzimas proteinase e fosfolipase, e a formação de franjas, antes e após a exposição às própolis e clorexidina. Dos 72 isolados, 53 eram C. albicans, 11 C. tropicalis, quatro C. guilhermondii e quatro sugestivas de C. dubliniensis. CFM 90% do extrato de própolis foi de 5% para C. albicans, 20% C. tropicalis, 0,625% C. guilhermondii e 0,312% sugestivas de C. dubliniensis. CFM 90% da clorexidina foi de 0,0018% para C. albicans, 0,012% C. tropicalis, de 0,0018% C. guilhermondii e de 0,00375% sugestivas de C. dubliniensis. Ocorreu inibição das exoenzimas e franjas, em ambos os produtos. Apesar da inibição da clorexidina ser menor que a da própolis, seu uso diário não causa efeitos colaterais indesejáveis como manchas nos dentes e na língua, perda do paladar e sensação de queimação na mucosa bucal.

The activity of propolis extract and chlorhexidine digluconate on Candida sp isolated from oral mucosa of patients in ICU was evaluated. The minimum fungicidal concentrations (MFC) were determined, and also the production of proteinase and phospholipase exoenzymes and the fringe formation. Seventy-two isolates were used and identified by the API 20C AUX® System. The antifungal activity was evaluated by “at base 2” serial microdilution technique. Also the exoenzymes production (proteinase and phospholipase), the fringes formation, before and after being exposed to propolis and chlorhexidine, were analysed. Of 72 isolates, 53 were C. albicans, 11 C. tropicalis, four C. guilhermondii and four suggestive C. dubliniensis. The MFC 90% of propolis extract was 5% C. albicans, 20% C. tropicalis, 0.625% C. guilhermondii; and 0.312% suggestive of C. dubliniensis. MFC 90% of chlorhexidine was 0.0018% C. albicans, 0.012% C. tropicalis, 0.0018% C. guilhermondii and 0.00375% suggestive of C. dubliniensis. The inhibition of exoenzymes and fringes occurred in the both products. Although the inhibition of chlorhexidine is lower than that showed by propolis, its daily use neither cause undesirable side effects as blemishes on the teeth and tongue, nor the loss of the taste and the burning sensation in the oral mucosa.

Anemia in nephrotic syndrome: approach to evaluation and treatment.

Nephrotic syndrome is one of the most common glomerular diseases that affect in children. Complications may occur in nephrotic syndrome as a result of the disease itself as well as its treatment. Most of these complications result from excessive urinary protein losses, and control of proteinuria is the most effective treatment strategy. Anemia is one of the many complications seen in patients with persistent nephrotic syndrome and may occur as a result of excessive urinary losses of iron, transferrin, erythropoietin, transcobalamin and/or metals. This leads to a deficiency of substrates necessary for effective erythropoiesis, requiring supplementation in order to correct the anemia. Supplementation of iron and erythropoietin alone often does not lead to correction of the anemia, suggesting other possible mechanisms which need further investigation. A clear understanding of the pathophysiologic mechanisms of anemia in nephrotic syndrome is necessary to guide appropriate therapy, but only limited evidence is currently available on the precise etiologic mechanisms of anemia in nephrotic syndrome. In this review we focus on the current state of knowledge on the pathogenesis of anemia in nephrotic syndrome.

Combination therapy with zinc gluconate and PUVA for alopecia areata totalis: an adjunctive but crucial role of zinc supplementation.

Spontaneous remission occurs in less than 10% of patients suffering from alopecia areata (AA) totalis for more than 2 years. The efficacy of PUVA therapy is controversial due to recurrence of hair loss after cessation. We report two cases presenting with AA totalis and AA universalis. After hair regrowth, relapse of hair loss occurred upon cessation of PUVA and zinc gluconate combination therapy. However, hair regrowth was noted upon the reintroduction of zinc gluconate and sulfur amino acids without PUVA in the first case and with episodic PUVA in the second case. The chronology of events appears to support the notion that zinc has a significant effect. Our findings suggest the possibility of a subgroup of zinc-responsive patients, but the identification of these patients remains difficult. Metallothioneins and zinc transporters regulating the entrance and exit of zinc in cells might play a key role. Combination therapy with immunomodulators may be administered to facilitate enhanced zinc-targeted action. Taking into account the safety profile of zinc, 30-40 mg/day of zinc metal may be used during at least 1 year, although we recommend to monitor its serum and hair levels. Studies with a larger number of patients are required to further investigate the therapeutic effect of zinc.

Effect of zinc supplementation on superoxide dismutase activity in patients with ulcerative rectocolitis / Efecto de la suplementación de zinc sobre la actividad de la enzima superóxido dismutasa (SOD) en pacientes con colitis ulcerosa

Introduction: Ulcerative rectocolitis is characterized by diffuse mucosal inflammation and oxidative stress. Thus, the organism activates the antioxidant defence system in an attempt to reduce the excessive production of reactive oxygen species or neutralize them. Objective: This study evaluated the effect of zinc supplementation on the activity of the enzyme superoxide dismutase (SOD) in patients with ulcerative rectocolitis. Methods: The study included 24 patients, aged between 20 and 59 years and diagnosed with ulcerative rectocolitis, in the remission stage of the disease, who were divided into two groups: experimental - deficient in zinc (n=12) and control - normal or high zinc (n=12). Only the first group underwent supplement intervention, in the form of zinc gluconate (30 mg Zn/day), taken daily in the morning, fasted for 60 days. Plasma and erythrocyte zinc concentrations were determined by flame atomic absorption spectrophotometer. The erythrocyte SOD activity was determined in vitro according to the methodology recommended by the manufacturer Randox. Results and Discussion: Zinc supplementation caused a significant increase in the plasma concentrations of the mineral, and showed a significant reduction in erythrocyte zinc, remaining within normal limits. The SOD activity was high in patients of both the experimental and control groups, with no difference after supplementation. Conclusion: This study demonstrates that zinc supplementation improves the homeostatic condition of the mineral, with no change in SOD activity, as a marker of oxidative stress in patients with ulcerative rectocolitis (AU)

Introducción: La colitis ulcerosa se caracteriza por la inflamación difusa de la mucosa y el estrés oxidativo. De esta forma, el cuerpo activa el sistema de defensa antioxidante en un intento de reducir la producción excesiva de especies reactivas de oxígeno, así como poder neutralizarlos. Objetivo: Este estudio evaluó el efecto de la suplementación de zinc sobre la actividad de la enzima superóxido dismutasa en pacientes con colitis ulcerosa. Métodos: El estudio incluyó 24 pacientes, con edades comprendidas entre 20 y 59 años y con diagnóstico de colitis ulcerosa en fase de remisión de la enfermedad. Los pacientes fueron divididos en dos grupos: experimental - deficiencia de zinc (n = 12) y control - normales o con altos contenido de zinc (n = 12). El grupo experimental se sometió a tratamiento con suplemento de drogas, en forma de gluconato de zinc (30 mg Zn / día), administrada diariamente por la mañana en ayunas durante 60 días. Las concentraciones en plasma y los eritrocitos de zinc se determinaron por espectrofotometría de absorción atómica de llama. La actividad de la superóxido dismutasa (SOD) se determinó por el método de eritrocitos in vitro utilizando el kit de Randox. Resultados y Discusión: La suplementación de zinc causó un aumento significativo en las concentraciones plasmáticas de mineral y mostró una reducción significativa en los eritrocitos, permaneciendo dentro de los límites normales. La actividad de SOD fue mayor en los pacientes de los grupos experimentales y de control, sin diferencias después de la suplementación. Conclusión: El estudio evidenció que la administración de suplementos de zinc mejora la condición homeostática del mineral, sin ningún cambio en la actividad de SOD, como un marcador de estrés oxidativo en pacientes con colitis ulcerosa (AU)

Effects of a phyto complex on well-being of climacteric women.

AIM: The aim of this study was to assess the effects of a phyto complex on menopausal symptoms. MATERIAL AND METHODS: A total of 151 women aged 42-67 years were enrolled. They were in spontaneous or surgical menopause by at least 12 months, reporting symptoms referable to the climacteric syndrome. Two validated and standardized tests were given to the whole sample at the entrance of the study (T0) and after 6 months of treatment (T6): the Greene Climacteric Scale (GCS) and the Beck Depression Inventory (BDI). Interim evaluations were carried out at 1-3 months (T1 and T3) on five symptoms selected from the GCS. The phyto complex was given to each enrolled woman, from the T0 to T6 time-points, for a total of 180 days. RESULTS: At the T0 time-point, the average scores were: GCS, 28.98 (standard deviation [SD] ± 10.71); BDI, 14.48 (SD ± 6.5). At the T1 time-point, five parameters of the GCS were assessed with a reduction of 36.25% in symptoms (5.69, SD ± 3.53). At the T6 time-point the assessment was completed: average GCS results were 11.54 (SD ± 8.01) with a 60.17% improvement; and average BDI results were 6.11 (SD ± 4.6) with a 58.91% improvement in the depressive symptoms. CONCLUSIONS: The phyto complex under consideration is an effective tool to counter, in a quick and long-lasting manner, the most common and nagging symptoms of the climacteric syndrome, such as hot flushes, insomnia and depression.

Medical treatment of traumatic anosmia.

OBJECTIVES: To study the effects of zinc and steroid in the treatment of traumatic anosmia. STUDY DESIGN: A prospective, randomized study. SETTING: Academic medical center. SUBJECTS AND METHODS: Patients with a clear history of loss of smell after head injury and whose thresholds were -1 measured by the phenyl ethyl alcohol threshold test were included in this study from January 2010 to May 2013. They were randomly divided into 4 groups. Patients in group 1 were treated with zinc gluconate for a month and high-dose prednisolone with tapering for 2 weeks. Those in group 2 took only zinc gluconate, and those in group 3 took only prednisolone. Patients in group 4 did not take any medicine. All patients were followed up by phenyl ethyl alcohol threshold testing, and magnetic resonance imaging was performed to measure the volume of olfactory bulbs. RESULTS: Thirty-nine patients in group 1, 35 in group 2, 34 in group 3, and 37 in group 4 completed the study. The recovery of olfactory function was observed in 11 patients (28.2%) in group 1, in 9 (25.7%) in group 2, in 4 (11.8%) in group 3, and in 1 (2.7%) in group 4. The recovery rates of olfactory function of groups 1 and 2 were significantly higher than the recovery rate of group 4. The volume of olfactory bulbs was not significantly different between those with and without improved olfactory function. CONCLUSION: Our results show that zinc gluconate has a promising effect in treating traumatic anosmia.

Effect of short term zinc supplementation on iron status of children with acute diarrhea.

OBJECTIVE: To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. METHODS: This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. RESULTS: Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 µg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 µg/dL post supplementation (p > 0.05). CONCLUSIONS: Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.

Zinc supplements for preventing otitis media.

BACKGROUND: Otitis media is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent otitis media. OBJECTIVES: To evaluate whether zinc supplements prevent otitis media in adults and children of different ages. SEARCH METHODS: We searched CENTRAL (2014, Issue 1), MEDLINE (1950 to February week 4, 2014) and EMBASE (1974 to March 2014). SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS: No new trials were identified for inclusion in this update. We identified 12 trials for inclusion, 10 of which contributed outcomes data. There were a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc-supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow-up (3191 participants); another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of otitis media (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias. AUTHORS' CONCLUSIONS: Evidence on whether zinc supplementation can reduce the incidence of otitis media in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition), but this is based on one small trial and should therefore be treated with caution.

Effect of zinc supplementation on superoxide dismutase activity in patients with ulcerative rectocolitis.

INTRODUCTION: Ulcerative rectocolitis is characterized by diffuse mucosal inflammation and oxidative stress. Thus, the organism activates the antioxidant defence system in an attempt to reduce the excessive production of reactive oxygen species or neutralize them. OBJECTIVE: This study evaluated the effect of zinc supplementation on the activity of the enzyme superoxide dismutase (SOD) in patients with ulcerative rectocolitis. METHODS: The study included 24 patients, aged between 20 and 59 years and diagnosed with ulcerative rectocolitis, in the remission stage of the disease, who were divided into two groups: experimental - deficient in zinc (n=12) and control - normal or high zinc (n=12). Only the first group underwent supplement intervention, in the form of zinc gluconate (30 mg Zn/day), taken daily in the morning, fasted for 60 days. Plasma and erythrocyte zinc concentrations were determined by flame atomic absorption spectrophotometer. The erythrocyte SOD activity was determined in vitro according to the methodology recommended by the manufacturer Randox. RESULTS AND DISCUSSION: Zinc supplementation caused a significant increase in the plasma concentrations of the mineral, and showed a significant reduction in erythrocyte zinc, remaining within normal limits. The SOD activity was high in patients of both the experimental and control groups, with no difference after supplementation. CONCLUSION: This study demonstrates that zinc supplementation improves the homeostatic condition of the mineral, with no change in SOD activity, as a marker of oxidative stress in patients with ulcerative rectocolitis.

Introducción: La colitis ulcerosa se caracteriza por la inflamación difusa de la mucosa y el estrés oxidativo. De esta forma, el cuerpo activa el sistema de defensa antioxidante en un intento de reducir la producción excesiva de especies reactivas de oxígeno, así como poder neutralizarlos. Objetivo: Este estudio evaluó el efecto de la suplementación de zinc sobre la actividad de la enzima superóxido dismutasa en pacientes con colitis ulcerosa. Métodos: El estudio incluyó 24 pacientes, con edades comprendidas entre 20 y 59 años y con diagnóstico de colitis ulcerosa en fase de remisión de la enfermedad. Los pacientes fueron divididos en dos grupos: experimental - deficiencia de zinc (n = 12) y control - normales o con altos contenido de zinc (n = 12). El grupo experimental se sometió a tratamiento con suplemento de drogas, en forma de gluconato de zinc (30 mg Zn / día), administrada diariamente por la mañana en ayunas durante 60 días. Las concentraciones en plasma y los eritrocitos de zinc se determinaron por espectrofotometría de absorción atómica de llama. La actividad de la superóxido dismutasa (SOD) se determinó por el método de eritrocitos in vitro utilizando el kit de Randox. Resultados y Discusión: La suplementación de zinc causó un aumento significativo en las concentraciones plasmáticas de mineral y mostró una reducción significativa en los eritrocitos, permaneciendo dentro de los límites normales. La actividad de SOD fue mayor en los pacientes de los grupos experimentales y de control, sin diferencias después de la suplementación. Conclusión: El estudio evidenció que la administración de suplementos de zinc mejora la condición homeostática del mineral, sin ningún cambio en la actividad de SOD, como un marcador de estrés oxidativo en pacientes con colitis ulcerosa.

Zinc for the common cold.

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.

Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis.

OBJECTIVE: We previously demonstrated that altered zinc homeostasis is an important feature of pediatric sepsis, thus raising the possibility of zinc supplementation as a therapeutic strategy in sepsis. Herein, we tested the hypothesis that prophylactic zinc supplementation would be beneficial in a murine model of peritoneal sepsis. DESIGN: Murine model of sepsis (intraperitoneal fecal-slurry injection). SETTING: Basic science research laboratory. SUBJECTS: C57BL/6 male mice. INTERVENTIONS: Intraperitoneal fecal-slurry injection, with or without zinc supplementation (10 mg/kg of intraperitoneal zinc gluconate for 3 days prior to intraperitoneal fecal-slurry injection). MEASUREMENTS AND MAIN RESULTS: Survival over 3 days following intraperitoneal fecal-slurry injection, markers of inflammation, bacterial load studies, and immunophenotyping studies. Zinc-supplemented mice demonstrated a significant survival advantage compared to control (nonsupplemented) mice. Zinc-supplemented mice also demonstrated moderate reductions of inflammation and immune activation. The survival advantage primarily correlated with reduced in vivo bacterial load in zinc-supplemented mice, compared to controls. In addition, peritoneal macrophages harvested from zinc-supplemented mice demonstrated a significantly enhanced phagocytosis capacity for Escherichia coli and Staphylococcus aureus, compared to peritoneal macrophages harvested from control mice. CONCLUSION: Prophylactic zinc supplementation reduces bacterial load and is beneficial in a murine model of peritoneal sepsis.

Zinc supplements for preventing otitis media.

BACKGROUND: Otitis media (OM) is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent OM. OBJECTIVES: To evaluate whether zinc supplements prevent OM in adults and children of different ages. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 1) which includes the Cochrane Acute Respiratory Infections Groups' Specialised Register, MEDLINE (1950 to February week 1, 2012) and EMBASE (1974 to February 2012). SELECTION CRITERIA: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing OM. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate. MAIN RESULTS: We identified 12 trials for inclusion, 10 of which contributed outcomes data. There was a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite OM during follow-up (3191 participants); another trial showed a significantly lower incidence rate of OM in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of OM (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias. AUTHORS' CONCLUSIONS: Evidence on whether zinc supplementation can reduce the incidence of OM in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition) but this is based on one small trial and should therefore be treated with caution.