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Zinc: Role in immunity, oxidative stress and chronic inflammation
Abstract
Zinc is essential for multiple cellular functions including immunity. Many investigators have used zinc supplementation in an attempt to affect the outcome of various diseases. These efforts were aimed at either supporting immunity by zinc administration or correcting the zinc dependent immune functions in zinc deficient individuals.
In this review, recent findings of zinc supplementation in various diseases have been presented. Beneficial therapeutic response of zinc supplementation has been observed in the diarrhea of children, chronic hepatitis C, shigellosis, leprosy, tuberculosis, pneumonia, acute lower respiratory tract infection, common cold, and leishmaniasis. Zinc supplementation was effective in decreasing incidences of infections in the elderly, in patients with sickle cell disease (SCD) and decreasing incidences of respiratory tract infections in children. Zinc supplementation has prevented blindness in 25% of the elderly individuals with dry type of AMD. Zinc supplementation was effective in decreasing oxidative stress and generation of inflammatory cytokines such as TNF-alpha and IL-1beta in elderly individuals and patients with SCD.
Zinc supplementation has been successfully used as a therapeutic and preventive agent for many conditions. Zinc functions as an intracellular signal molecule for immune cells.
... It is involved in a wide variety of cellular functions, including enzymes of intermediate metabolism, cell membrane function, and gene expression [11]. It has also been described that Zn can regulate the inflammation process, through several mechanisms such as inhibiting the NFκB and JAK2/STAT3 pathways, which in turn decrease IL-6 and leptin formation [12,13]. Due to its role in the metabolism, Zn homeostasis at the cellular level is sophisticatedly regulated by transporter proteins, which are divided into two classes: Zn transporters (ZnT) and Zrt-Irt-like protein (ZIP). ...
... This family of proteins acts in such a way that they bind to Zn and do not allow it to be transported within the cell. Thus, MT can also act as a "Zn buffer"; through their low affinity binding, they provide labile Zn for protein or enzyme use when Zn concentration is limited [13,14]. ...
... In processes of acute inflammation, Zn concentrations undergo redistribution in tissues, probably due to an increased demand for Zn-dependent proteins in inflammatory conditions, which could affect serum Zn levels and, in turn, the expression of Zn transporters in other tissues [15,16]. For example, Zn status determines the activation of NFκB, which is a key inflammatory mediator that regulates the expression of proinflammatory cytokines, chemokines, and acute phase proteins [11,13]. Several studies have revealed that Zn supplementation in humans significantly reduced serum inflammatory and oxidative stress markers [17]. ...
The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r = − 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.
... (9,10) Zinc plays an essential role in many biochemical pathways as a cofactor for more than 300 enzymes, such as the expression of several genes, and in immune function regulation in many types of cells. (11,12) A cohort study by Chen et al. (13) showed that an adequate nutritional zinc intake was associated with lower CAD mortality. Moreover, a systematic review by Ranasinghe et al. (6) revealed that zinc supplementation significantly reduced total cholesterol, LDLC, and triglycerides. ...
... It has been reported that lower zinc intake is associated with CAD (29) and CAD mortality. (13) Furthermore, a systematic review by Ranasinghe et al. (11) revealed that zinc supplementation significantly reduced TC, LDLC, and TG. Therefore, improvements in HDLC and LDLC reduce the risk of CAD, indicating that the high zinc intake in the dyslipidaemic group decreased the risk of developing CAD. ...
Although the relationship between dyslipidaemia (DL) and coronary artery disease (CAD) or between trace minerals intake and CAD is well known separately, the exact nature of this relationship remains unknown. We hypothesize that the relationship between trace mineral intake and CAD may differ depending on whether or not the individual has DL. The present study analysed the relationships among trace mineral intake, DL, and CAD in middle-aged and older adults living in Shika town, Ishikawa prefecture, Japan. This study included 895 residents following the exclusion of those with genetic risk carriers for familial hypercholesterolemia. Trace mineral intake was evaluated using the brief-type self-administered diet history questionnaire. Interactions were observed between DL and CAD with zinc ( p = 0.004), copper ( p = 0.010), and manganese intake ( p < 0.001) in a two-way analysis of covariance adjusted for covariates such as sex, age, body mass index, and current smokers and drinkers. Multiple logistic regression analysis showed that zinc (odds ratio (OR): 0.752; 95% confidence interval (CI): 0.606, 0.934; p = 0.010), copper (OR: 0.175; 95% CI: 0.042, 0.726; p = 0.016), and manganese (OR: 0.494; 95% CI: 0.291, 0.839; p = 0.009) were significant independent variables for CAD in the dyslipidaemic group. The present results suggest that DL with a low trace mineral intake is associated with CAD. Further longitudinal studies are required to confirm this relationship.
... These findings suggest that reduced levels of these metal ions contribute to PMN dysfunction in response to aging. Deficiencies in Zn 2+ , Ca 2+ , and other micronutrients are well-known issues in elderly subjects [60], which can contribute to immune dysregulation, reduced clearance of extracellular ATP, and inflammatory PMN responses [40,[60][61][62][63][64]. Clinical studies have shown that Zn 2+ supplementation can significantly reduce the risk of infections in elderly individuals [61,62,65]. ...
... Deficiencies in Zn 2+ , Ca 2+ , and other micronutrients are well-known issues in elderly subjects [60], which can contribute to immune dysregulation, reduced clearance of extracellular ATP, and inflammatory PMN responses [40,[60][61][62][63][64]. Clinical studies have shown that Zn 2+ supplementation can significantly reduce the risk of infections in elderly individuals [61,62,65]. We found that Zn 2+ is essential for the activity of plasma ATPases in mice. ...
Background
The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals.
Results
Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca²⁺, Mg²⁺, and Zn²⁺, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging.
Conclusions
Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.
... In terms of the immunomodulation, some research suggests that zinc plays an important role in maintenance of balanced intestinal mucosal immune, which mainly involved the regulation of T cells. It has been found that zinc deficiency can lead to an imbalance of T cell subsets and promote inflammatory reactions, which can then exacerbate the pathological severity of IBD [51][52][53]. Increased Th17 cells and decreased Tregs were observed in IBD patients [54][55][56], while physiological zinc Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
... However, little is known about the effect of zinc levels on macrophages and DCs in IBD, which need to be further researched. It seems that researchers have overlooked the study of zinc intervention on the specific immune function of IBD animals, although many studies found that zinc deficiency or IBD decreased the production of thymulin and induced the decrease and subset-unbalance of T cells [51,58,86,112,113]. ...
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract (GI) with a high incidence rate globally, and IBD patients are often accompanied by zinc deficiency. This review aims to summarize the potential therapeutic value of zinc supplementation in IBD clinical patients and animal models. Zinc supplementation can relieve the severity of IBD especially in patients with zinc deficiency. The clinical severity of IBD were mainly evaluated through some scoring methods involving clinical performance, endoscopic observation, blood biochemistry, and pathologic biopsy. Through conducting animal experiments, it has been found that zinc plays an important role in alleviating clinical symptoms and improving pathological lesions. In both clinical observation and animal experiment of IBD, the therapeutic mechanisms of zinc interventions have been found to be related to immunomodulation, intestinal epithelial repair, and gut microbiota’s balance. Furthermore, the antioxidant activity of zinc was clarified in animal experiment. Appropriate zinc supplementation is beneficial for IBD therapy, and the present evidence highlights that alleviating zinc-deficient status can effectively improve the severity of clinical symptoms in IBD patients and animal models.
... Для поддержания и функционирования иммунной системы детей важное значение придается обеспеченности витаминами и минеральными веществами, которые играют ключевую роль на каждом этапе иммунного ответа [2][3][4][5][6]. Наиболее значимую роль играют витамины A, D, E, C, B6, B12 и минеральные вещества, такие как железо (Fe), цинк (Zn), медь (Cu), селен (Se) и магний (Mg), которые взаимодополняют друг друга, поскольку имеют сходные механизмы действия [7][8][9][10][11][12]. ...
... 2) мы рекомендуем продолжать постоянной прием в профилактической дозе (табл. 1) для поддержания оптимального уровня витаминов и минеральных веществ у детей с рекуррентными респираторными инфекциями, как это рекомендуется «Национальной программой по оптимизации обеспеченности витаминами и минеральными веществами детей России», 2017 г. 4 Поступила / Received 01.12.2023 Поступила после рецензирования / Revised 19.12.2023 ...
Introduction. Recurrent respiratory infections in children are a pressing problem in pediatrics. To maintain and function the immune system in children, their provision of vitamins and minerals is important.
Purpose. To assess the provision of children with recurrent respiratory infections with vitamins (A, E, D, C, B 6 , B 12 , folic acid) and minerals (Zn, Fe, Mg, Ca, P) and to correct their deficiency with a vitamin-mineral complex.
Materials and methods. The study was conducted on 65 children aged 3 to 8 years in 2 groups of children: group 1, children with RID, n = 50; group 2 – control, n = 15). An outpatient examination, a parent survey and a blood test for vitamins (A, E, D, C, B 6 , B 12 , folic acid) and minerals (Zn, Fe, Mg, total Ca, Ca++, P) were carried out. 30 children with RID were prescribed the vitamin and mineral complex, 1 tablet 2 times a day, with an assessment of vitamin and mineral sufficiency and the frequency of respiratory infections after the end of the dose.
Results. In all examined children, both in the main and control groups, the most common were deficiencies of fat-soluble vitamins D (69%), A (40%), E (35%) and the minerals Zn (70%) and Fe (44%). In children with RID, deficiency of vitamins D, A and Zn was more common than in the control group (p < 0.05), in 96% of cases it was combined, more often in the form of a combined deficiency of fat-soluble vitamins D, A, E and minerals Zn, Fe (66% of cases). Taking vitamin-mineral complex in the 2 nd prophylactic dose for 1 month contributed to an improvement in vitamin and mineral sufficiency and a decrease in respiratory morbidity in the next 2 months after stopping the drug.
Conclusion. Vitamin-mineral complex can be successfully used to maintain vitamin and mineral levels and reduce respiratory morbidity in children with recurrent respiratory infections.
... Дефіцит цинку впливає на функціонування макрофагів (фагоцитоз), на дозрівання і функціонування Т-і Вклітин [11], що відбувається внаслідок дизрегуляції основних біологічних функцій на клітинному рівні. Секреція і функціонування цитокінівосновних месенджерів імунної системи -зменшується за умов дефіциту цинку [11,12], а це збільшує ризики виникнення багатьох вірусних захворювань, пневмонії та малярії. Відомо, що препарати із цинком є ефективним засобом у лікуванні звичайної застуди, за умови їх використання не пізніше, ніж за 24 години після появи перших ознак хвороби [13]. ...
... Споживання цинку гальмує розвиток вірусних інфекцій. Відомо, що він сприяє терапевтичним інтервенціям у лікуванні ВІЛ/СНІДу, а також корисний у терапії інших вірусних інфекцій [11,12,13,14]. Екзогенне введення цинку пригнічує реплікацію вірусу COVID-19 в клітині [30,31]. ...
The important role of zinc in living organisms is mediated by its participation in many physiological processes. It is present in all tissues, organs, and secretions of the human body and is one of the most essential and important trace elements for the human body. This trace element is essential for catalytic activity and is a structural component of about 200 metalloenzymes involved in various metabolic pathways (DNA and RNA polymerases, dehydrogenases, carboxypeptidases, phosphatases, superoxide dismutases, alcohol dehydrogenases, pyruvate carboxylases, and many others). The biological role of zinc in the human body is largely realised in the processes of energy metabolism, in the synthesis and stabilisation of nucleic acids and proteins, in maintaining the antioxidant status, cell proliferation and differentiation. According to WHO estimates, about 31% (from 4 to 73%) of the world's population suffer from zinc deficiency. Zinc deficiency in the human body can occur for many reasons, including malnutrition, impaired absorption in the intestinal mucosa, inadequate or impaired binding of zinc to albumin, poor absorption of zinc by cells, competition with other metals, a high-fibre diet that impairs zinc absorption, disorders of transferrin synthesis, pancreatic function, diarrhoea, etc. A decrease in the zinc content in the body is accompanied by impaired chemotaxis of polymorphonuclear lymphocytes, natural killer cells, slowing down phagocytosis, and the activity of calprotectin production mechanisms. In order to correct metabolic disorders in various diseases caused by zinc deficiency in the human body, it is proposed to use a mixture for the preparation of an oxygen cocktail enriched with zinc ions, which allows for specific prevention and correction of zinc deficiency states and has an immunomodulatory effect.
... This result is consistent with the findings of Nacamulli et al., who indicated that selenium supplementation can reduce thyroid antibody levels in patients with Hashimoto's disease [25]. Similarly, zinc plays a crucial role in supporting the immune system and hormone production, as confirmed by Prasad [26]. ...
Background: The thyroid gland plays a crucial role in regulating metabolism and various bodily functions through hormone production. Women are particularly susceptible to thyroid disorders such as hypothyroidism and Hashimoto’s disease, with associated symptoms affecting overall well-being. Prior research has inadequately addressed the influence of dietary habits and nutritional knowledge on thyroid health, especially in women. Objective: This study aimed to evaluate the dietary habits and nutritional awareness of women aged 18–45 with diagnosed thyroid disorders, emphasizing the effects of education level on knowledge and dietary practices. Material and Methods: A cross-sectional survey was conducted with 297 women diagnosed with thyroid conditions. The survey assessed demographics, comorbidities, hydration habits, and knowledge about nutrient intake critical for thyroid health. Chi-square tests, ANOVA, and correlation analyses were performed to evaluate associations. Results: Hypothyroidism and Hashimoto’s disease were most prevalent among younger women (18–25 years). A significant association was observed between higher education and knowledge of protein and carbohydrate roles in managing thyroid health (p < 0.01). Women with higher educational backgrounds more frequently used healthier cooking methods and were more informed about beneficial nutrients, including vitamin D and omega-3. A chi-square test indicated that low water intake was significantly associated with comorbid conditions, including insulin resistance and cardiovascular disease (p < 0.01). Conclusions: Significant gaps remain in dietary knowledge, particularly concerning protein intake and nutrient–drug interactions, indicating a need for targeted dietary education. Women with higher education demonstrated greater dietary awareness, emphasizing the importance of tailored educational interventions to enhance thyroid disorder management.
... Deficiencies in these vitamins have been associated with various oral manifestations, including glossitis, megaloblastic anemia and mucosal inflammation 10,11 . While the exact mechanism by which zinc and B vitamin supplementation led to rapid improvement in this case is unclear, several possibilities exist: 12 1. Correction of underlying nutritional deficiencies 2. Anti-inflammatory effects of zinc 3. Enhanced epithelial regeneration and wound healing 4. Modulation of local immune responses The response to supplementation in this case suggests that nutritional factors may play a more significant role in the pathogenesis and management of geographic tongue than previously recognized. However, it is important to note that this is a single case, and larger controlled studies are needed to establish the efficacy of this approach. ...
Background: Geographic tongue is a benign inflammatory condition characterized by erythematous patches on the tongue surface. While often self-limiting, it can cause discomfort and concern for patients. Nutritional deficiencies have been implicated in its etiology, but effective treatments remain limited. Case Presentation: A 23-year-old male from Rajshahi, Bangladesh presented to Update Dental College with asymptomatic erythematous patches on his tongue, consistent with geographic tongue. The patient had no significant medical history or known nutritional deficiencies. Methods: Based on potential associations with zinc and B vitamin deficiencies, the patient was prescribed daily zinc sulfate and a vitamin B complex supplement. Follow-up was scheduled after one week. Results: At 15 days follow-up, clinical examination revealed near-complete resolution of the erythematous patches. The patient reported no adverse effects from the supplementation and expressed satisfaction with the outcome. Conclusion: This case demonstrates rapid improvement of geographic tongue with zinc and vitamin B complex supplementation. While further research is needed, this approach may offer a promising treatment option for some patients with geographic tongue, potentially by addressing underlying nutritional deficiencies. Update Dent. Coll. j: 2024; 14(2): 36-37
... There are several possible mechanisms for the observed difference in mortality risk between the higher and lower serum zinc levels based on its involvement in various biological processes as a cofactor of more than 300 enzymes that regulate metabolism [7], blood pressure control [9,10], immune function [11], anti-oxidative mechanisms [12], and vascular calcification [13]. A meta-analysis of 15 randomized controlled trials of zinc supplementation for patients undergoing maintenance hemodialysis showed increases in serum zinc levels and dietary protein intake and improved inflammatory markers including CRP, superoxide dismutase, and malondialdehyde [27]. ...
Background/Objectives: Zinc is an essential microelement, and its deficiency is common in patients undergoing hemodialysis. However, the association between serum zinc and mortality in these patients remains unclear. The aim of this study was to explore the possible association between serum zinc levels and all-cause mortality in prevalent patients with kidney failure on maintenance hemodialysis. Methods: This was a prospective cohort study of maintenance hemodialysis patients followed up for 5 years. The key exposure was serum zinc level measured at baseline, and the outcome was all-cause mortality. Their association was analyzed using Cox proportional hazard models. Results: Among 1662 eligible patients selected for this analysis, 468 (28%) died. Lower serum zinc levels were associated with a higher risk for mortality, independent of the major demographic factors and factors including mineral and bone disorder and renal anemia. However, this association was no longer significant when adjusted for serum albumin. Because there was a close correlation between serum zinc and albumin levels, we performed further analyses in which participants were categorized into four groups by median serum zinc (68 µg/dL) and albumin (3.7 g/dL) levels. In the lower serum albumin groups, risk of death was significantly higher in those with lower zinc than those with higher zinc levels, whereas such a difference was not significant in the high serum albumin groups. Conclusions: In patients undergoing maintenance hemodialysis with lower serum albumin levels, a lower serum zinc level was associated with a higher risk of mortality.
... Severe deficiency of Zn is rare, and the most common cause is a genetic predisposition [93]. Zinc deficiency has been associated with increased oxidative damage to lipids, proteins and DNA [94]. Animal studies have shown that a prolonged deficiency of Zn leads to oxidative stress. ...
Despite the efforts made by the World Health Organization to create prevention programs and strategies for heavy metal poisoning, some of these are still frequent, mainly in some work areas. Its effects can range from minimal to lethal for humans, depending on the exposure time and the dose. The health professional is an essential point of contact to detect possible exposure and intoxication with any of these heavy metals, so knowing their symptoms and mechanism of action, metabolism, and treatment is of the utmost importance. In this brief article, some of the most important points to consider as healthcare personnel are summarized.
... In addition to protein, certain micronutrients like zinc, which is required for immune system function, oxidative stress response, and wound healing, can help speed up the healing process. [26] ...
A gastric ulcer, also known as a stomach ulcer, is a breach in the mucous membranes' normal integrity that extends into the muscularis mucosa, the submucosa, or deeper. Acid secretion, and therefore the pH of the contents of the oesophagus, stomach, and duodenum, as well as the pH of the gastric wall, is well recognised to play a major role in the development of ulcer disease. Understanding the processes of acid secretion and acid resistance has taken a lot of study in order to be able to cure ulcer disease. Acid secretion, bacteria and their products, non steroidal anti-inflammatory medications, alcohol, reactive oxygen species, and different chemical substances are only a few of the variables that might modify the epithelial barrier and stimulate the creation of mucosal damage. We should eat a well-balanced diet if we have a peptic ulcer. Whatever diet is used to treat a peptic ulcer, it must be nutritionally adequate first and foremost.
... Thus, therapeutic targets which aim to fight against the ROS become an important strategy. Zinc is an essential micronutrient crucial for immune system physiology, acting as a signaling molecule, anti-inflammatory agent, and antioxidant that stabilizes cell membranes [139]. On the other hand, zinc oxide nanoparticles (ZnO NPs) also proved to exhibit potent antioxidant properties. ...
Chronic inflammation underpins many severe diseases, often requiring anti-inflammatory drugs that can have adverse effects. Medicinal herbs offer an alternative but suffer from poor solubility, limiting their efficacy. Nanotechnology, particularly zinc oxide nanoparticles (ZnO NPs), presents a promising solution to enhance the therapeutic potential of herbal compounds. This review examines the nature and benefits of ZnO NPs in drug delivery systems compared to other nanomaterials. It highlights the advantages of biogenic synthesis of ZnO NPs, detailing the eco-friendly formation mechanisms and common characterization methods. The anti-inflammatory effects of biosynthesized ZnO NPs over the last five years are comprehensively reviewed, with insights into their mechanisms of action. Additionally, the pharmacokinetic and toxicokinetic profiles of ZnO NPs are explored to understand their biokinetics post-drug release. In conclusion, biogenically synthesized ZnO NPs enhance the bioavailability of medicinal plant compounds, offering a compelling alternative for treating inflammatory conditions.
... Being micronutrients as more than 1,000 cofactors of enzymatic reactions, its role in various functions in the structure and regulation of the human body makes zinc (Zn 2+ ) one of the essential minerals needed by the body [3]. Estimated that there are more than 2 billion humans who have a zinc deficit which leads to health problems such as growth retardation, neurodegenerative diseases, and immune system damage [4]. ...
Zinc supplements currently marketed in Indonesia are second-generation zinc supplements, which must be improved for the effectiveness caused by their low absorption rate and side effects on the gastrointestinal tract. Third-generation zinc supplements are currently being investigated to improve the effectiveness of the previous generation of supplements. The present study aimed to discover a new alternative source of zinc-chelating peptide (ZCP) from Holothuria scabra. In addition, the research investigates the ZCP characteristics and absorption abilities in an ex vivo evaluation using the everted gut sac model method. The results obtained were six zinc peptides: Asp-Asp-Ala- Phe-Gln-Ala-Phe-Cys; Thr-Asp-Asn-Leu; Leu-Gly-Cys; Pro-Gly-Thr; Ser-Cys; and Pro-Tyr. The characterization showed that the resulting peptides comprised two to eight amino acids with molecular weights between 208 and 915 Da. The highest zinc binding capacity of the peptides was 92.11 mg/100 g at 30 kDa for molecular weight. Fourier-transform infrared spectra indicate that zinc ions (Zn2+) bind to carboxyl groups and interact with nitrogen atoms in amino acids and amides. The scanning electron microscope-energy dispersion spectroscopy results stated that, topographically and morphologically, ZCP has a different surface with peptides with Zn composition in the sample. Furthermore, we evaluated the peptide fractions for ex vivo absorption in the small intestine using the everted gut sac method. We found that zinc-binding peptides transported and enhanced zinc absorption in the duodenum segment at 60 minutes, resulting in a 40% increase in absorption rate. The potency of ZCPs from H. scabra as an alternative to third-generation zinc supplements with higher absorption than previous-generation supplements.
... [29][30][31] Zinc, an essential trace element, plays a pivotal role in managing oxidative stress, growth regulation, and immune function by modulating inflammatory cytokines. 32,33 Research has underscored the healing potential of zinc phosphate (ZnP) as a foundational material in mitigating pulp inflammation. 34 Combining nanoparticles formulated from L-Arg, CaP, and ZnP (L-(CaP-ZnP) NPs) presents an intriguing prospect. ...
Background
Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue.
Methods
The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP–AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining.
Results
In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin.
Conclusion
The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.
... In addition to dietotherapy and the nutrients highlighted above, zinc and selenium can help accelerate healing. While zinc is essential in maintaining the immune system functions [32], selenium, on the other hand, helps to reduce disease complications and improve the healing process [33]. ...
Purpose of review: The management of Peptic Ulcer Disease (PUD) is achieved using pharmacological agents to counteract the aggressive factors or stimulate the mucosal defence. In recent years, plant-based bioactive products have gained popularity as an alternative management protocol due to the increased antibiotic resistance of Helicobacter pylori (H. pylori), lower cost, perceived effectiveness, availability, and little side effects. In this review, we summarized the conventional treatment methods, alternative bioactive compounds, and the dietotherapy of PUD.
Recent findings: The conventional management methods include antacids, gastric muscle stimulants, mucosal-increasing resistance agents, antisecretory medications (anticholinergic agents),
and Proton Pump Inhibitors (PPIs). Most of the plant’s bioactive compounds are alkaloids, terpenes, flavones, isoflavones, flavonols, chalcones, flavanones, xanthones, flavan-3-ols, anthocyanins, and capsaicinoids. These bioactive compounds work in a dose-dependent manner and express their therapeutic functions through pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), and Interleukin-6 (IL-6), resulting in a reduction in prostaglandin E2. No food product has a history of causing the PUD, but some foods are prohibited or need to be taken with caution. Some of these food items, such as spicy foods, caffeine, and alcohol, can hinder healing and worsen the symptoms while fibres, vitamins C and A, zinc, iron, and selenium can promote healing.
Conclusion: While there are limited articles in the literature to elucidate the dietotherapy of PUD, a balanced diet should always be provided in this course to manage the pathology. The paucity of this information opens up more research opportunities in PUD dietotherapy.
... Studies have highlighted zinc's ability to facilitate epithelial cell turnover, enhance fibroblast proliferation, and support the formation of granulation tissue [66]. Zinc's anti-inflammatory properties have been widely documented, with studies showing its ability to modulate immune responses and inhibit pro-inflammatory cytokines like IL-1β and TNF-α [67,68]. ...
Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.
... Zinc is fundamental for the development of the cell-mediated innate immune system and functions as an antioxidant and anti-inflammatory molecule [53]. Limited trials have evaluated the use of zinc in the management of rosacea, and of the available studies, findings have been inconsistent. ...
Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.
... The common approaches include chemical or physical destruction of the affected tissue, enhancement of the local immune response, and antiproliferative therapy. [6,7] Zinc is an essential micronutrient having a wide spectrum of actions. The zinc deficiency adversely affects the immune function, especially, T cell functions. ...
Background
Warts are cutaneous manifestations of human papillomavirus (HPV). Trauma and maceration facilitate initial epidermal inoculation. The spread may then occur by autoinoculation. Local and systemic immune factors appear to influence the spread. Zinc is an essential micronutrient having a wide spectrum of actions. Deficiency of the same adversely affects the immune function, especially, T cell functions. The role of zinc as an immunological modulator activates lymphocytes and cytokines against the penetration and replication of viruses, which has increasingly been recognized. Numerous skin disorders have been linked to zinc deficiency. A high dose of oral zinc sulfate has shown outstanding therapeutic efficacy and prevents relapse in patients with recalcitrant and multiple warts. Owing to the therapeutic efficacy of oral zinc in the treatment of warts, the current study was undertaken to find out the association between serum zinc level and multiple cutaneous warts among the study population.
Materials and methods
One hundred and ten patients with cutaneous warts met the inclusion criteria and an equal number of age and sex-matched controls were enrolled. A consecutive sampling technique was used for the enrolment. Details regarding the duration, number, clinical type, size, and distribution of the warts were recorded. Serum zinc levels were estimated in both cases and controls. Data were tabulated and analyzed using the SPSS software version 20.
Results
The reference range for normal serum zinc levels was taken as 60–180 µg/dL. Normal serum zinc levels were found in 91 (100%) of the cases and 100 (110%) of the controls; high levels were found only in 9 (10%) of the cases. Cases were found to have significantly higher mean serum zinc levels compared with the controls. (121.1 ± 35.78 µg/dL vs. 101.8 ± 20.48µg/dL, P = 0.0001).
Conclusion
Patients with multiple cutaneous warts were found to have higher mean serum zinc levels compared with age and sex-matched controls. There was no significant association of serum zinc levels with the duration or the number of warts.
... The beneficial effects of therapeutic zinc supplementation have been observed in a variety of infections, including diarrhea and acute lower respiratory tract infections [24,28], 2 major causes of morbidity and death in children < 5 y in LMICs [29]. Preventive zinc supplementation in LMICs reduces the incidence of diarrhea, may decrease the incidence of acute lower respiratory tract infections, and reduces child mortality [30][31][32]. ...
Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is, thus, vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related noncommunicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zinc’s role in health, the impact of the changing climate and global context on zinc intake, novel functional biomarkers showing promise for monitoring population-level interventions, and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combating global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions, including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent.
... Instead, lower levels of Zn promote crucial cellular processes such as adhesion, proliferation, migration, and DNA damage repair, and enhance the expression of F-actin and adhesion protein. Numerous studies have verified that Zn, as an antioxidant, reduces ROS production and protects proteins from free radicals, showing an outstanding performance in anti-oxidative stress [34][35][36]. ...
Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cells’ (ECs) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production, and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/L. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.
... Moreover, the correlation between the lower quartile of circulating micronutrient patterns, as explained by Zn, Mg, Ca, and K, and an increase in HOMA-IR, may be attributed to their antioxidant and anti-inflammatory activity. The management of oxidative stress and low-grade inflammation, often observed in this population, contributes to the binding of insulin to the receptor and the phosphorylation of its substrates (Chausmer 1998;Prasad 2009;Jomova et al. 2022). ...
The circulating micronutrient pattern in type 2 diabetes mellitus (T2DM) may impact glycemic control and insulin resistance; however, there is a scarcity of studies that have evaluated the circulating micronutrient pattern in the T2DM population. Therefore, our objective was to identify circulating micronutrient pattern and their association with markers of glycemic control and insulin resistance in individuals with T2DM. We developed a cross-sectional observational study involving adults with T2DM in Sergipe, Brazil. We assessed plasma levels of magnesium, zinc, calcium, potassium, and serum 25-hydroxyvitamin D. Additionally, also measured fasting glucose levels, the percentage of glycated hemoglobin (%HbA1c), and calculated the homeostatic model assessment for insulin resistance (HOMA-IR). Patterns of body reserve were established using principal component analysis and categorized into quartiles. Binary logistic regression models were employed. We evaluated 114 individuals (63.7% women), with a median age and body mass index of 49 years and 29.6 kg/m², respectively. Two circulating micronutrient patterns were identified, explaining 62.5% of the variance: Pattern 1 (positive contributions from magnesium, zinc, calcium, and potassium) and Pattern 2 (positive contributions from 25-hydroxyvitamin D and zinc, with a negative contribution from potassium). Lowest quartile for Pattern 1 and Pattern 2 exhibiting a 4.32-fold (p = 0.019) and 3.97-fold (p = 0.038) higher likelihood of increasing HOMA-IR and %HbA1c values, respectively, compared to the larger quartiles. However, no associations were found between these patterns and fasting glucose values. Lowest quartile for both patterns of micronutrients was associated with inadequate metabolic control in individuals with T2DM.
... Additionally, a decrease in the production of cytokines, particularly IL-6, has been documented [8]. Zinc serves a dual role in biological systems, acting as both an anti-inflammatory molecule and an antioxidant that aids in the stabilization of cellular membranes [9]. ...
The COVID-19 (Coronavirus Disease 2019) outbreak has not yet ended and poses a persistent hazard to individuals, communities, and healthcare systems globally. Similar to numerous other diseases, the immune system of the patient is intricately associated with the advancement and mortality rates of COVID-19. In general, the immune system plays a crucial role in protecting the host against infections and neoplastic cells, and a well-balanced diet can enhance the immune system's ability to effectively defend against infectious agents. There have been suggestions that the administration of zinc supplements may decrease the occurrence of lower respiratory tract infections in children who are deficient in zinc. This study will thus examine the potential of zinc as a preventive and therapeutic agent, either on its own or in conjunction with other techniques, as zinc fulfills all the requirements outlined above. The study cohort was stratified into three distinct groups, namely critical care patients, service patients, and a healthy control group; a total of 24 COVID-19 patients in critical care, 27 ward-treated COVID-19 patients, and 26 healthy individuals. The groups exhibited a notable disparity in age distribution (p<0.001). A statistically significant difference was seen among the groups in relation to the survey results, presence of chronic disease, and length of hospital stay (p<0.001, p<0.001, and p=0.007, respectively). COVID-19 patients (n=51) exhibited markedly reduced zinc levels in comparison to a control group of healthy individuals (n=26). It was observed that the average zinc level in patients diagnosed with COVID-19 was 89 μg/dl (range: 43-123 μg/dl). In comparison, the median zinc level in individuals without COVID-19 was found to be 99.5 μg/dl (range: 79-125 μg/dl). A statistically significant difference was observed between the groups (p=0.023). The study revealed that a total of 13 individuals, accounting for 25.5% of the COVID-19 patients, exhibited a deficiency in zinc levels. The findings of our study indicate that zinc potentially plays a significant role in the context of COVID-19. However, additional research is required to get a comprehensive understanding of the association between COVID-19 and zinc.
... As a result, a decrease in minerals like copper and zinc may result in insufficiency of copper and/or zinc metalloenzymes, which are involved in the antioxidant defense system [29]. Zinc serves as an indirect antioxidant, so concurrent dietary inadequacy and/ or deficiency may contribute to the occurrence of a variety of diseases, complicate clinical features, negatively affect the immunologic status, increase oxidative stress, and increase the production of inflammatory cytokines [8,26]. Under oxidative stress conditions, iron mediates the formation of superoxide anion radicals and hydrogen peroxide, which oxidize cellular macromolecules and membrane proteins [12]. ...
Sixty-one horses were enrolled in this study and divided into 3 different groups according to their severity of colic (heart rate, oral mucous membrane color, and abdominal distention): a strangulating colic (SC) group (n=21), non-strangulating colic (NC) group (n=20), and control group (n=20) consisting of randomly selected normal horses without signs of colic. The serum concentrations of haptoglobin, tumor necrosis factor-α (TNFα), nitric oxide (NO), malondialdehyde (MDA), zinc, iron, and copper were evaluated in all horses. The average concentration of TNFα in the SC group was higher than that in the control group (P<0.001). The TNFα concentration was higher in the NC group compared with the control group (P<0.001). Furthermore, the average concentration of TNFα tended to be higher in the SC group compared with the NC group (P=0.052). The average concentration of haptoglobin in the SC group was higher than that in the control group (P<0.001). The average concentration of NO was higher in the SC group compared with the NC group. (P=0.016) The average concentration of MDA was higher in the SC group compared with the control group (P=0.042). Furthermore, the concentration of MDA was higher in the SC group compared with the NC group (P=0.048). TNFα in horses with signs of colic may be a reliable indicator of prognosis and the severity of clinical signs. The haptoglobin concentration may be a useful marker in cases where animals are referred to clinicians a few days after the onset of colic. The concentrations of MDA and NO should be interpreted with caution.
... Multiple studies have been performed investigating a potential benefit of Zn 2+ supplementation on immune function (10,(20)(21)(22). Some suggest Zn 2+ supplementation to have a beneficial effect as a supportive cancer treatment (23)(24)(25). ...
Background
Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Currently, multimodality treatment including chemotherapy with cisplatin or carboplatin in combination with pemetrexed offers the best options. Detoxification of heavy metals in the cell by metallothioneins (MT) is associated with early failure to platin-based chemotherapy. The induction of MTs gene expression or its enzyme results in saturation by exposure to metal ions such as zinc or cadmium. Its therapeutically effect is still not analyzed in depth.
Methods
In our study, we investigated three MPM cell lines and one fibroblast cell line in the course of cisplatin treatment and supplementation of zinc. Cell state analyses via an enzyme-activity based assay were performed. With this, we were able to analyze apoptosis, necrosis and viability of cells. Additionally, we tested treated cells for changes in metallothionein IIA (MT2A) expression by using quantitative realtime polymerase chain reaction.
Results
Zinc supplementation induces gene expression of MT2A. Overall, a zinc dose-dependent induction of apoptosis under platin-based treatment could be observed. This effect could be verified in all analyzed cell lines in varying intensity.
Conclusions
MT expression is induced by zinc in a dose-dependent manner and inhibits a successful cisplatin therapy. Therefore, heavy metal exposure during cisplatin therapy, e.g., via cigarette smoke, might be an important factor. This should be considered in further therapeutic approaches.
... Zinc regulates the growth and functioning of epithelial cells and leucocytes (Read et al., 2019). Moreover, it regulates the generation of T cells, cytokines, and reactive oxygen species (ROS) (Prasad, 2009;Tanumihardjo et al., 2016). In addition, zinc stimulates appetite. ...
Urinary tract infection (UTI) is responsible for a significant portion of the overall expenses of health care as well as mortality rates globally. We searched through the available research to evaluate whether micronutrient supplements affect the frequency and intensity of UTI in children Papers that investigated the effects of vitamins D and C, zinc, and multiple micronutrient supplementations (MMS) on the incidence and severity of UTI in pediatric patients were pooled together. A random effects model was used to conduct a meta-analysis of data. Vitamin D supplementation reduced the risk of UTI and shortened the duration of symptoms in children. If a clinical diagnosis or laboratory investigation was used to confirm UTI, the relative probability of UTI with vitamin D was remote from the null than using the self-report. If vitamin C was administrated, the frequency of UTI was reduced, and the period of clinical manifestations was cut to half. It was not possible to determine the impact of using zinc supplements. According to the findings of the current review, taking micronutrient supplements such as zinc, vitamins C and D, and multiple micronutrient supplementation could assist in preventing UTI and lessen its clinical outcome in pediatric patients. More research is required to establish the effect of individual or combination of micronutrients on the treatment outcomes of UTI.
... In addition to protein, particular micronutrients such as zinc, which is required to sustain immune system function, respond to oxidative stress, and repair wounds [25], can help to speed up the healing process. Selenium has been shown to minimize infection complications and enhance healing [10]. ...
Peptic ulceration is a lesion of the upper gastrointestinal tract's mucosal lining that involves a disparity of proactive and defensive mucosal components, with Helicobacter pylori as the primary causative cause. Dietary supplements are useful in the prevention and treatment of this condition. The goal of this study is to enhance the use of nutritional supplements for persons with peptic ulcers. A non-restricted exploratory review was conducted using firsthand information from the Scielo, PubMed, Medline, ISI, and Scopus databases. Dietotherapy and energy dispersion should be tailored to the patient's needs in order to normalize nutritional status and facilitate healing. The recommended nutrition alters between the acute and repair stages, with the recovery phase requiring more protein and several micronutrients such as vitamin A, zinc, selenium, and vitamin C. Furthermore, several studies have suggested that vitamin C can aid in the eradication of H. pylori. Fibers and probiotics are particularly important in the treatment of peptic ulcers because they lessen antibiotic adverse effects and assist shorten treatment time. A nutritious diet is essential in the cure of peptic ulcers since food can prevent, treat, or even alleviate symptoms associated with this illness. Nevertheless, there are few publications that reinvent dietotherapy; so, new investigations addressing more particularly dietotherapy for peptic ulcer treatment are required.
... Mice treated with ZnO nanoparticles exhibited signs of toxicity, including weight loss, passive behavior, and reduced survival [5]. Zinc, as an indispensable trace element, holds crucial significance in facilitating the proper functioning of several enzymes involved in maintaining the balance between the interplay between oxidative and antioxidative mechanisms [6]. Zinc is increasingly recognized for its involvement in the immune system, particularly in supporting the normal development and proper functioning of cells involved in immune responses and acting as a second messenger. ...
This research study investigated the structural features involved in
synthesizing an alginate-ZnO nanocomposite with anti-inflammatory
activity. Chemically synthesized ZnO nanoparticles (NPs) were combined
with sodium alginate to produce a nanocomposite. The formation of the
nanocomposites was confirmed through various analytical techniques,
including ATR infrared spectroscopy, high-resolution field emission scanning
electron microscopy, and X-ray diffraction analysis. The anti-inflammatory
effect of Alg-ZnO NCs administered orally as a preventive measure was
assessed by measuring the percentage of inhibition of edema induced by
carrageenin in mice. Alg-ZnO demonstrated significant inhibition of
carrageenan-induced paw edema.
... Dietary supplementation of different Zn sources in the current study improved the serum antioxidant status (SOD and TAC levels) with no significant effect between ZnO NPs and control groups. The improvement in blood antioxidant status may be due to zinc being considered an effective antioxidant by having catalytic, coactive, or structural functions in different enzymes such as SOD, which controls many physiological processes such as metabolism and immune function 73 , or by inhibiting the oxidation of macromolecules such as DNA and proteins 17 or by maintaining the activities of radical scavenging enzymes 40 . The improvement in blood antioxidant status may be associated to the enhancing in seminal antioxidant status as mentioned earlier in our study, which illustrated that zinc prevents the oxidative damage to the sperm cells and thereby improve the fertility 11 . ...
The harmful influences of global warming on rabbit reproduction and industry attract global attention. Zinc (Zn) is an important trace element with a wide list of functions in the male reproductive system. The aim of this study was to estimate the effects of different forms of zinc supplementation, as organic (Zn methionine), nano (nano Zn oxide) as indirect way to minimized it impact on environment, and inorganic (Zn sulphate) on physiological parameters, semen quality, anti-oxidative status, hormonal profiles of male rabbits subjected to server heat stress. Thirty-six V-line bucks (6–7 months old, 2842.29 ± 34.46 g weight) were randomly distributed to 4 groups, bucks in 1st group (control group, Con) fed basal diet without Zn supplementation, the 2nd, 3rd and 4th groups fed basial diet with 30 mg/kg of zinc methionine (Zn-Met), nano zinc oxide (ZnO-NPs), and zinc sulphate (Zn-S), respectively for a period of 10 weeks suffered from severe heat stress of environmental ambient temperature (over 32 of temperature humidity index, THI). Semen samples were collected and evaluated for volume, pH, motility, concentration, viability, initial fructose, and seminal plasma antioxidant concentration. Liver, kidney function, hormonal and antioxidant profile were measured in blood serum. The results revealed that, compared to control, all forms of Zn supplementation used significantly improved kidney function (creatinine), serum antioxidant (SOD and CAT), physiological parameters, especially on 1st month of the experiment, and seminal plasma antioxidant (SOD and CAT) of heat stressed bucks. Likewise, semen quality in terms of sperm concentration, sperm viability, and initial fructose enhanced significantly (P ≤ 0.05) by ZnO-NPs supplementation. Zinc methionine supplementation significantly improved liver function and decreased seminal plasma TBARs. Treatments with Zn-Met and ZnO-NPs increased seminal TAC and blood testosterone levels with reduced blood cortisol levels compared to other groups. Severe heat stress could be counteract by inclusion Zn with studied forms Zn-Met and ZnO-NPs at recommended dose (30 mg/kg diet) to improve semen quality and antioxidant status.
... It is an essential mineral for diabetic patients because of its involvement in insulin integrity. Additionally zinc helps to improve the microcirculation and enhances the process of ulcer and wound healing 40 . Several studies evaluated the influence of zinc ions on the anti inflammatory activity and the beneficial effects of zinc ions on the anti edematous and gastric activity of NSAIDs 41 . ...
Zinc oxide nanoparticles are widely used in medical and pharmaceutical industries. They are known for their role in molecular imaging, drug delivery, diagnosis and treatment of various diseases. Zinc oxide nanoparticles synthesised using plant extract will be eco-friendly, simple and reliable methods offering therapeutic options which are safe, free of side effects and effective for a wide range of diseases. In our study we have chosen Andrographis Paniculata and Phyllanthus niruri which are widely used in Ayurveda for various systemic problems. Transmission electron microscopes can be used for understanding the characteristics of the synthesised nanoparticles. The aim of the present study is to perform transmission electron microscopy analysis of zinc oxide nanoparticles prepared using herbal formulation. Collection of Andrographis paniculata and Phyllanthus niruri plant and preparing its extract followed by the synthesis of zinc oxide nanoparticles using the prepared herbal formulation. The stable zinc oxide nanoparticles were characterised by UV-Vis spectroscopy from 300nm to 700nm. The nanoparticle solution was centrifuged and the final putrefied nanoparticle pellet is collected and stored in an airtight eppendorf tube. The nanoparticles are analysed for its morphological character using TEM. The zinc oxide nanoparticles prepared using the herbal formulation were characterised by UV-Vis spectroscopy, which showed shift peak at the range 350nm to 550nm. The synthesised nanoparticle had spherical shaped grain like morphology and the particle sizes distributed are in the average range of 10-60nm. This simple and eco friendly biological approach for the formation of ZnO nanoparticles has a promising application in medical sciences.
... Zn can only be absorbed through the diet [3]. However, Zn deficiency has become a global problem and affects human health [4] due to regional and dietary differences. A study by Wessells [5] was performed to estimate the global prevalence of Zn deficiency and indicated that insufficient dietary Zn intake may be quite common worldwide. ...
Zinc (Zn) is an important trace element in the human body and plays an important role in growth, development, and male reproductive functions. Marginal zinc deficiency (MZD) is common in the human population and can cause spermatogenic dysfunction in males. Therefore, the aim of this study was to investigate methods to improve spermatogenic dysfunction caused by MZD and to further explore its mechanism of action. A total of 75 4-week-old male SPF ICR mice were randomly divided into five groups (control, MZD, MZD + ZnY2, MZD + ZnY4, and MZD + ZnY8, 15 mice per group). The dietary Zn content was 30 mg/kg in the control group and 10 mg/kg in the other groups. From low to high, the Zn supplementation doses administered to the three groups were 2, 4, and 8 mg/kg·bw. After 35 days, the zinc content, sperm quality, activity of spermatogenic enzymes, oxidative stress level, and apoptosis level of the testes in mice were determined. The results showed that MZD decreased the level of Zn in the serum, sperm quality, and activity of spermatogenic enzymes in mice. After Zn supplementation, the Zn level in the serum increased, sperm quality was significantly improved, and spermatogenic enzyme activity was restored. In addition, MZD reduced the content of antioxidants (copper-zinc superoxide dismutase (Cu–Zn SOD), metallothionein (MT), and glutathione (GSH) and promoted malondialdehyde (MDA) production. The apoptosis index of the testis also increased significantly in the MZD group. After Zn supplementation, the level of oxidative stress decreased, and the apoptosis index in the testis was reduced. Furthermore, quantitative real-time polymerase chain reaction (qRT–PCR) showed that the expression of B-cell lymphoma-2 (Bcl-2) mRNA and Bcl-2/BCL2-associated X (Bax) in the control group decreased in testicular cells, and their expression was restored after Zn supplementation. The results of this study indicated that Zn supplementation can reduce the level of oxidative stress and increase the ability of testicular cells to resist apoptosis, thereby improving spermatogenic dysfunction caused by MZD in mice.
... In inducing several cellular functions, such as cell division, protein synthesis, and DNA replication [8] . Zn deficiency can deteriorate both innate and adaptive immunity [9] . In biological systems, Zn exists only as Zn 2þ [10] . ...
Background/Objectives: Foot-and-mouth disease (FMD) remains a significant global threat to livestock farming. Current commercial FMD vaccines present several challenges, including the risk of infection and adverse injection site reactions due to oil-based adjuvants. The complex immune environment of the gut-associated lymphoid tissue has the potential to induce broad and diverse immune responses. Therefore, we aimed to explore the potential of zinc sulfate as an oral adjuvant to enhance intestinal mucosal immunity and complement the effects of intramuscular (IM) FMD vaccination. Methods: We conducted serological analyses on mice and pigs, measuring secretory IgA (sIgA) levels and evaluating the expression of mucosal immunity-related genes in pigs. These assessments were used to investigate the systemic and mucosal immune responses induced by oral zinc sulfate administration in combination with an IM FMD vaccine. Results: This combination strategy significantly increased structural protein antibody titers and virus neutralization titers in experimental animals (mice) and target animals (pigs) across early, mid-, and long-term periods. Additionally, this approach enhanced the expression of key cytokines associated with mucosal immunity and increased sIgA levels, which are critical markers of mucosal immunity. Conclusions: Oral zinc sulfate administration may synergize with inactivated FMD vaccines, leading to sustained and enhanced long-term immune responses. This novel strategy could reduce the frequency of required vaccinations or allow for a lower antigen dose in vaccines, effectively stimulating the mucosal immune system and boosting systemic immunity. This approach has the potential to improve the overall efficacy of commercial FMD vaccines.
Background
It has been reported that zinc deficiency is related to severe inflammatory conditions especially those of respiratory diseases. However, studies that have examined the association between the serum zinc concentration and the severity of coronavirus disease 2019 (COVID-19) are still limited. The aim of this study was to assess that association in Japanese inpatients with COVID-19.
Methods
This cross-sectional study, conducted from April 2020 to August 2021, included 467 eligible adult inpatients with COVID-19 whose serum zinc concentration was measured. Serum zinc concentration categories were defined as deficiency (< 60 μg/dL), marginal deficiency (≥ 60 to < 80 μg/dL), and normal (≥ 80 μg/dL). Multivariate logistic regression was used to assess the association between serum zinc deficiency and severe COVID-19. Serum zinc concentration levels were compared between mild and other severities of COVID-19 by Dunnett’s method. The P for trend was estimated using the Jonckheere-Terpstra test.
Results
The proportions of subjects with serum zinc deficiency (< 60 μg/dL) and marginal zinc deficiency (≥ 60 to < 80 μg/dL) were 39.5% and 54.3% in women, and 36.4% and 57.0% in men, respectively. Serum zinc deficiency was significantly associated with severe COVID-19 compared to marginal deficiency and normal (odds ratio = 3.60, 95% confidence interval = 1.60–8.13, P < 0.01) after adjusting for confounders. An increase in severity of COVID-19 was inversely related to increases in serum zinc concentration levels (P < 0.01 for trend). Each serum zinc concentration of moderate and severe cases was also significantly lower compared with mild cases (P < 0.01).
Conclusion
The severity of COVID-19 was significantly related to serum zinc concentration levels. These results suggest the importance of considering the serum zinc concentration when treating patients with COVID-19.
Periodized nutrition matches macronutrient intake with different training phases-preparation, competition, and recovery-to support glycogen replenishment, muscle repair, and overall recovery. Research shows that consuming high-glycemic carbohydrates immediately after exercise helps replenish glycogen and reduce muscle fatigue. Similarly, taking easily digestible proteins like whey within 30 minutes after exercise boosts muscle protein synthesis and repair through the mTOR pathway. Omega-3 fatty acids also aid recovery by lowering exercise-induced inflammation and supporting joint health. Key micronutrients like magnesium, zinc, and Vitamins C and E help recovery by reducing oxidative damage and supporting immune function. This review discusses how periodized nutrition can manage stress by regulating cortisol and serotonin levels, improving mood, and reducing stress.
In this study, fluorescent gold nanoclusters (AuNCs) conjugated with pyridoxal-5-phosphate (PLP) were synthesized, characterized, and used for Zn²⁺ fluorescence turn-on sensing. PLP was conjugated over the surface of papain-stabilized fluorescent gold nanoclusters (pap-AuNCs; λex = 380 nm, λem = 670 nm) by forming imine linkage. Due to this modification, the red color emitting pap-AuNCs changed to orange color emitting nanoclusters PLP_pap-AuNCs. The nano-assembly PLP_pap-AuNCs detect Zn²⁺ selectively by showing a notable fluorescence enhancement at 477 nm. Zn²⁺ detection with PLP_pap-AuNCs was quick and easy, with an estimated detection limit of 0.14 µM. Further, paper strips and cotton buds coated with PLP_pap-AuNCs were developed for affordable on-site visual detection of Zn²⁺. Finally, the detection of Zn²⁺ in actual environmental water samples served as validation of the usefulness of PLP_pap-AuNCs.
In the intricate realm of respiratory health, allergic airways diseases stand as a significant challenge, affecting millions globally with conditions such as asthma and allergic rhinitis, and pose substantial challenges to individuals and healthcare systems worldwide. In the intricate tapestry of human health, the respiratory system stands as a sentinel of life, facilitating the exchange of vital gases and ensuring the sustenance of every cell. Yet, this intricate machinery is not immune to disruptions, and among the myriad challenges it faces, allergic airways diseases emerge as significant contenders. Asthma and allergic rhinitis, two prominent entities within this spectrum, orchestrate a symphony of immunological responses that, when dysregulated, induce chronic inflammation, and compromise respiratory function. Amid the quest for innovative therapeutic strategies, the application of metal and metal oxide nanoparticles emerges as a promising frontier of exploration. This chapter endeavors to unravel the dynamic interplay between allergic airways diseases and the therapeutic potential of metal and metal oxide nanoparticles, delving into the underlying mechanisms, recent advancements, and the promising prospects for future clinical applications in this evolving field.
Cardiovascular health is a hot topic around the world, and as the incidence of cardiovascular disease increases each year, people are increasingly focusing on the management of their heart health. Dietary and lifestyle changes as non-pharmacological treatments have been increasingly recognized as important in the prevention of cardiovascular disease and in reducing the risk of cardiovascular accidents. Awareness of different nutrients and their effects on cardiovascular health is important for establishing a good dietary pattern. This review summarizes the effects of the five major nutrients in the daily diet, namely carbohydrates, proteins, dietary fats, vitamins, and minerals, on cardiovascular health, and aims to provide a more comprehensive understanding of the effects of a healthy dietary pattern on cardiovascular health.
Non-alcoholic fatty liver disease (NAFLD) is a condition in which the pathological cumu-lation of fat with coexisting inflammation and damage of hepatic cells leads to progressive dysfunc-tions of the liver. Except for the commonly well-known major causes of NAFLD such as obesity, dyslipidemia, insulin resistance, or diabetes, an unbalanced diet and imbalanced nutritional status should also be taken into consideration. In this narrative review, we summarized the current knowledge regarding the micro-and macronutrient status of patients suffering from NAFLD considering various diets and supplementation of chosen supplements. We aimed to summarize the knowledge indicating which nutritional impairments may be associated with the onset and progression of NAFLD at the same time evaluating the potential therapy targets that could facilitate the healing process. Except for the above-mentioned objectives, one of the most important aspects of this review was to highlight the possible strategies for taking care of NAFLD patients taking into account the challenges and opportunities associated with the micronutrient status of the patients. The current research indicates that a supplementation of chosen vitamins (e.g., vitamin A, B complex, C, or D) as well as chosen elements such as zinc may alleviate the symptoms of NAFLD. However, there is still a lack of sufficient data regarding healthy ranges of dosages; thus, further research is of high importance in this matter.
Background: Close contacts may develop subclinical leprosy with no symptoms but with M. leprae in their blood. Zinc is said to help in the prevention of M. leprosy infection. This study aimed to determine the correlation between zinc (Zn) serum levels and IgM anti PGL-1 levels in household contacts of multibacillary type leprosy patients. Methods: This study is cross-sectional and involves 48 leprosy subjects (33 multibacillary leprosy household contact and 15 non-contact subjects). Subjects were selected based on the inclusion and exclusion criteria. Zinc and IgM anti PGL-1 levels were derived from venous blood examined with ELISA. Results: This study showed the mean serum zinc level of the contact groups of 60.88 ± 15.92 μg/dl and the non-contact group of 90.00 ± 7.61 μg / dl (p <0.001; CI 95%: 20.38 - 37.85). The median (interquartile range) serum levels of IgM anti PGL-1 in the contact groups was 613.00 (40 - 1433) u/ml and the non-contact groups was 99.00 (14 - 695) u/ml (p = 0.001; 95% CI: 154.162 – 610.116). The correlation analysis between serum zinc levels and IgM anti PGL-1 serum levels r= 0.644 (p<0.05). A high serum zinc level is a protective factor against high IgM anti PGL-1 levels in household contact with leprosy (PR: 0.47; 95% CI: 0.20-1.09). Conclusion: Zinc levels negatively correlate with IgM anti PGL-1 levels in subjects with household contact with multibacillary type leprosy. A high serum zinc level protects against high IgM anti PGL-1 levels.
Background
Chronic kidney disease (CKD) patients might be zinc deficient due to compromised nutritional intake and dietary protein restrictions; protein foods being rich in zinc. Zinc deficiency might cause increased oxidative stress and consequently reduced antioxidant parameters. Tailored dietary counseling along with zinc supplementation may play a major role in affecting the zinc and antioxidant status of patients.
Aim
The aim of this study was to investigate the effect of zinc supplementation and dietary counseling on oxidative stress and antioxidant parameters in CKD patients.
Materials and Methods
185 subjects were enrolled for the study (145 were predialysis patients [Group-1 (Stage-3 CKD) and Group-2 [Stage-4 CKD]) on the basis of Kidney Disease Outcomes Quality Initiative CKD stages from 1 to 5; and 40 apparently healthy controls. Zinc supplementation alone (Intervention 1) was given to 50 CKD patients (30 Group-1 and 20 Group-2). Diet counseling (Intervention 2) consisted of 45 patients (25 Group-1; 20 Group-2). 50 patients (30 Group-1 and 20 Group-2) received both zinc supplementations along with diet counseling (Intervention 3). Dietary zinc status, oxidative stress and antioxidants were accessed for all subjects.
Results
Intervention-1 and 3 groups exhibited highly significant improvement in antioxidant status and lowering of oxidative stress.
Conclusion
Improving zinc status through dietary counseling and supplementation may help in combating enhanced oxidative stress by improving antioxidant parameters in renal failure patients.
Essential metals play critical roles in maintaining human health as they participate in various physiological activities. Nonetheless, both excessive accumulation and deficiency of these metals may result in neurotoxicity secondary to neuroinflammation and the activation of microglia and astrocytes. Activation of these cells can promote the release of pro-inflammatory cytokines. It is well known that neuroinflammation plays a critical role in metal-induced neurotoxicity as well as the development of neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Initially seen as a defense mechanism, persistent inflammatory responses are now considered harmful. Astrocytes and microglia are key regulators of neuroinflammation in the central nervous system, and their excessive activation may induce sustained neuroinflammation. Therefore, in this review, we aim to emphasize the important role and molecular mechanisms underlying metal-induced neurotoxicity. Our objective is to raise the awareness on metal-induced neuroinflammation in neurological disorders. However, it is not only just neuroinflammation that different metals could induce; they can also cause harm to the nervous system through oxidative stress, apoptosis, and autophagy, to name a few. The primary pathophysiological mechanism by which these metals induce neurological disorders remains to be determined. In addition, given the various pathways through which individuals are exposed to metals, it is necessary to also consider the effects of co-exposure to multiple metals on neurological disorders.
Trichinellosis is a re-emerging worldwide foodborne zoonosis. Oxidative stress is one of the most common detrimental effects caused by trichinellosis. In addition, Trichinella infection poses an infinite and major challenge to the host’s immune system. Resistance and side effects limit the efficiency of the existing anti- trichinella medication. Given that concern, this work aimed to investigate the anti-helminthic, antioxidant, anti-inflammatory and immunomodulatory effects of resveratrol and zinc during both phases of Trichinella spiralis infection. Sixty-four Swiss albino mice were divided into four equal groups: non-infected control, infected control, infected and treated with resveratrol, and infected and treated with zinc. Animals were sacrificed on the 7th and 35th days post-infection for intestinal and muscular phase assessments. Drug efficacy was assessed by biochemical, parasitological, histopathological, immunological, and immunohistochemical assays. Resveratrol and zinc can be promising antiparasitic, antioxidant, anti-inflammatory, and immunomodulatory agents, as evidenced by the significant decrease in parasite burden, the significant improvement of liver and kidney function parameters, the increase in total antioxidant capacity (TAC), the reduction of malondialdehyde (MDA) level, the increase in nuclear factor (erythroid-derived 2)-like-2 factor expression, and the improvement in histopathological findings. Moreover, both drugs enhanced the immune system and restored the disturbed immune balance by increasing the interleukin 12 (IL-12) level. In conclusion, resveratrol and zinc provide protection for the host against oxidative harm and the detrimental effects produced by the host’s defense response during Trichinella spiralis infection, making them promising natural alternatives for the treatment of trichinellosis.
Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms against pathogens and the delicate balance of pro-and anti-inflammatory regulation in the long term. Generally, a well-balanced diet is capable of providing the necessary minerals to support the immune system. Nevertheless, specific vulnerable populations should be cautious about obtaining adequate amounts of minerals such as magnesium , zinc, copper, iron, and selenium. Inadequate levels of these minerals can temporarily impair immune competence and disrupt the long-term regulation of systemic inflammation. Therefore, comprehending the mechanisms and sources of these minerals is crucial. In exceptional circumstances, mineral deficiencies may necessitate supplementation; however, excessive intake of supplements can have adverse effects on the immune system and should be avoided. Consequently, any supplementation should be approved by medical professionals and administered in recommended doses. This review emphasizes the crucial significance of minerals in promoting optimal functioning of the immune system. It investigates the indispensable minerals required for immune system function and the regulation of inflammation. Moreover, it delves into the significance of maintaining an optimized intake of minerals from a nutritional standpoint.
A selenium-containing metal-organic framework with remarkable antioxidant capacity and ROS-scavenging activity was constructed by a controlled de novo encapsulation approach of a glycoconjugate mimetic, specifically a sp2-iminoglycolipid bearing a selenoureido fragment (DSeU), within a zeolitic-imidazolate framework exoskeleton. Biocompatible and homogeneous nanosized particles of ∼70 nm (DSeU@ZIF8) were obtained, which could be efficiently internalized in cells, overcoming the poor solubility in biological media and limited bioavailability of glycolipids. The ZIF-particle served as nanocarrier for the intracellular delivery of the selenocompound to cells, promoted by the acidic pH inside endosomes/lysosomes. As demonstrated by in vitro studies, the designed DSeU@ZIF8 nanoparticles displayed a high antioxidant activity at low doses; lower intracellular ROS levels were observed upon the uptake of DSeU@ZIF8 by human endothelial cells. Even more interesting was the finding that these DSeU@ZIF8 particles were able to reverse to a certain level the oxidative stress induced in cells by pre-treatment with an oxidizing agent. This possibility of modulating the oxidative stress in living cells may have important implications in the treatment of diverse pathological complications that are generally accompanied with elevated ROS levels.
Background:
Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss.
Objective:
To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.
Design:
The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo.
Main outcome measures:
(1) Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (> or =15 letters). Primary analyses used repeated-measures logistic regression with a significance level of.01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring.
Results:
Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations.
Conclusions:
Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study.
Diets deficient in zinc cause rapid atrophy of the thymus and loss of T-cell helper function in the young adult A/J mouse. Because zinc deficiency, as well as other nutritional deficiences, causes extensive damage to the immune system, the question arose as to whether zinc-deficient mice could repair the thymus and fully regenerate T-cell helper function if returned to diets containing adequate amounts of zinc. Five-week-old A/J female mice were fed either a zinc-deficient (<1 mug of Zn per g) or a zinc-adequate (50 mug of Zn per g) diet for 31 days. Histological examination of thymuses from the zinc-deficient mice revealed that the cortex was preferentially involuted and the thymus was about one-third of normal size. The direct plaque-forming cells produced per mouse spleen in response to immunization with sheep erythrocytes was 34% of normal; indirect plaque-forming cells were 18% of normal (Jerne plaque assay). After the deficient mice had been fed a zinc-adequate diet for 1 week, their response was nearly normal, except that the indirect response was 68% of controls; in this same period, the thymuses of these mice had quadrupled in size and exhibited a greatly enlarged cortex repopulated with immature thymocytes. By 2 weeks, the thymuses of the previously zinc-deficient mice were normal in size and appearance; however, there was a slight increases in numbers of indirect plaque-forming cells. By 4 weeks, the thymus weights, direct and indirect plaque-forming cell counts, and secondary response of the previously deficient mice were normal. Mice that were nearly athymic after 45 days of dietary zinc deficiency were also able to fully reconstruct the thymus and regenerate T-cell helper function. The data show that the zinc-deficient young adult mouse has the capacity to fully restore the T-cell-dependent antibody-mediated responses upon nutritional repletion.
Serum zinc and copper levels and zinc/copper ratios were studied in 86 healthy controls, 45 cases of borderline tuberculoid (BT), 31 cases of borderline lepromatous (BL), 117 cases of lepromatous (LL) leprosy patients, 16 cases with severe erythema nodosum leprosum (ENL) reaction, and 16 cases with ENL reaction receiving oral zinc therapy. A significant reduction in serum zinc levels was noticed in all types of leprosy, the maximum decrease being seen in cases with ENL reaction. Conversely, the copper levels were significantly increased from BT to LL cases with ENL reaction in a progressive manner. A very good negative correlation (r = -0.998) was noticed between mean serum zinc and copper levels from healthy controls to active LL cases with ENL reaction. After oral zinc therapy, the serum zinc levels were significantly increased in all of the 16 LL patients with ENL reaction. In contrast, the copper levels were not decreased, indicating that oral zinc therapy can restore normal zinc levels in leprosy patients but is unable to reduce the increased copper levels.
The molecular mechanism of the effects of zinc ions against herpes simplex virus (HSV) infection was investigated. Zinc sulphate (100 microM) in the culture medium of an HSV-infected African green monkey kidney cell line did not block viral DNA synthesis and, at this concentration, only moderate cytotoxic effects were observed in uninfected cells. Nevertheless, virus yields were reduced to less than 1% of the control. Thus the long standing hypothesis that zinc might block multiplication of HSV by selective intranuclear inhibition of the viral DNA polymerase apparently has lost its validity. Inhibition of virus growth in the absence of severe cytotoxicity must therefore result from other effects of ZnSO4. Free virus is inactivated by 15 mM-ZnSO4 within a few hours of its addition. The inactivated virus is defective in the glycoprotein-dependent functions of penetration and, to some extent, adsorption. Electron micrographs show massive deposition of zinc onto virion components. In a virion, transmembrane transport of zinc ions is not expected and the established antiviral effect is therefore explained by an inhibition of virion glycoprotein function after non-specific accumulation of zinc into many virion membrane components.
The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions.
The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment.
Our goal was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status.
In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antituberculosis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment.
At baseline, 64% of patients had a body mass index (in kg/m(2)) < 18.5, 32% had plasma retinol concentrations < 0.70 micromol/L, and 30% had plasma zinc concentrations < 10.7 micromol/L. After antituberculosis treatment, plasma zinc concentrations were not significantly different between groups. Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo (P < 0.05). Sputum conversion (P < 0.05) and resolution of X-ray lesion area (P < 0.01) occurred earlier in the micronutrient group.
Vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion.
Several studies showed benefits of long-term zinc supplementation on the incidence, severity, and duration of diarrhea and on the incidence of respiratory infections. Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children.
We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis.
A randomized, double-blind, placebo-controlled trial was conducted in Shigella-infected children aged 12-59 mo. Elemental zinc (20 mg) and a multivitamin containing vitamins A and D, thiamine, riboflavin, nicotinamide, and calcium at twice the recommended dietary allowance were given daily for 2 wk to the zinc group (n = 28), whereas the multivitamin alone was given to the control group (n = 28). Standard antibiotic therapy was given to all patients.
Serum zinc concentrations increased in both groups during convalescence; however, zinc supplementation showed a significant effect. The lymphocyte proliferation response in the zinc group increased relative to that in the control group (P = 0.002), but no significant effects were seen on concentrations of cytokines (interleukin 2 and interferon gamma) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines (interleukin 2, interferon gamma, and interleukin 1beta) in feces. Among the antigen [lipopolysaccharide and invasion plasmid-encoded antigen (Ipa)]-specific antibodies, plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group. However, the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool.
A 14-d course of zinc supplementation during acute shigellosis increases the lymphocyte proliferation response and the Ipa-specific immunoglobulin G response.
Zinc is lost during diarrheal diseases, and zinc deficiency induces intestinal morphology-altering inflammatory responses that zinc supplementation can correct.
We assessed the in vivo effect of zinc supplementation on systemic and mucosal responses in mildly to moderately malnourished (defined as <-1 but >-2 and <-2 but >-3 weight-for-height z scores, respectively, based on the National Center for Health Statistics growth reference) children with shigellosis.
A double-blind placebo-controlled trial was conducted in Shigella flexneri-infected children aged 12-59 mo. Daily for 14 d, elemental zinc (20 mg) and multivitamins (vitamins A and D, thiamine, riboflavin, and nicotinamide) plus calcium were given at twice the US recommended dietary allowance to the zinc group (n=28), and multivitamins plus calcium were given to the control group (n=28). All subjects received standard antibiotic therapy.
There was no significant interaction between zinc supplementation and time, but zinc supplementation showed a significant effect on serum zinc concentrations. With a >or=4-fold increase in serum shigellacidal antibody titers from baseline used as the cutoff, the proportion of children with shigellacidal antibody response was greater in the zinc group than in the control group (P<0.03). There was a significant (P=0.02) treatment x time interaction for the proportions of circulating CD20+ and CD20+CD38+ cells, which were higher on day 7 in the zinc group than in the control group (P<0.007). No effect was seen on histopathologic features or the expression of innate and inflammatory mediators in the rectum.
Adjunct therapy with zinc during acute shigellosis significantly improved seroconversion to shigellacidal antibody response and increased the proportions of circulating B lymphocytes and plasma cells.
Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence.
We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol.
The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001).
Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea.
Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.
Zinc deficiency, cell-mediated immune dysfunction, susceptibility to infections, and increased oxidative stress have been observed in elderly subjects (ie, those >55 y old). Zinc is an effective antiinflammatory and antioxidant agent.
The primary objective was to determine the effect of zinc on the incidence of total infections in healthy elderly subjects. The secondary objective was to determine the effect of zinc on cytokines and oxidative stress markers.
A randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in elderly subjects. Fifty healthy subjects of both sexes aged 55-87 y and inclusive of all ethnic groups were recruited for this study from a senior center. The zinc-supplemented group received zinc gluconate (45 mg elemental Zn/d) orally for 12 mo. Incidence of infections during the supplementation period was documented. The generation of inflammatory cytokines, T helper 1 and T helper 2 cytokines, and oxidative stress markers and the plasma concentrations of zinc were measured at baseline and after supplementation.
Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules. The incidence of infections and ex vivo generation of tumor necrosis factor alpha and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group. Plasma zinc and phytohemagglutin-induced interleukin 2 mRNA in isolated mononuclear cells were significantly higher in the zinc-supplemented than in the placebo group.
After zinc supplementation, the incidence of infections was significantly lower, plasma zinc was significantly higher, and generation of tumor necrosis factor alpha and oxidative stress markers was significantly lower in the zinc-supplemented than in the placebo group.
Zinc plays an important role in immune function. The association between serum zinc and pneumonia in the elderly has not been studied.
The objective was to determine whether serum zinc concentrations in nursing home elderly are associated with the incidence and duration of pneumonia, total and duration of antibiotic use, and pneumonia-associated and all-cause mortality.
This observational study was conducted in residents from 33 nursing homes in Boston, MA, who participated in a 1-y randomized, double-blind, and placebo-controlled vitamin E supplementation trial; all were given daily doses of 50% of the recommended dietary allowance of essential vitamins and minerals, including zinc. Participants with baseline (n = 578) or final (n = 420) serum zinc concentrations were categorized as having low (<70 microg/dL) or normal (>or=70 microg/dL) serum zinc concentrations. Outcome measures included the incidence and number of days with pneumonia, number of new antibiotic prescriptions, days of antibiotic use, death due to pneumonia, and all-cause mortality.
Compared with subjects with low zinc concentrations, subjects with normal final serum zinc concentrations had a lower incidence of pneumonia, fewer (by almost 50%) new antibiotic prescriptions, a shorter duration of pneumonia, and fewer days of antibiotic use (3.9 d compared with 2.6 d) (P <or= 0.004 for all). Normal baseline serum zinc concentrations were associated with a reduction in all-cause mortality (P = 0.049).
Normal serum zinc concentrations in nursing home elderly are associated with a decreased incidence and duration of pneumonia, a decreased number of new antibiotic prescriptions, and a decrease in the days of antibiotic use. Zinc supplementation to maintain normal serum zinc concentrations in the elderly may help reduce the incidence of pneumonia and associated morbidity.
Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial.
Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5.
Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P < .0001) and shorter durations of cough (2.1 vs. 5.0 days; P < .0001) and nasal discharge (3.0 vs. 4.5 days, P = .02) Blinding of subjects was adequate, and adverse effects were comparable in the 2 groups. Symptom severity scores were decreased significantly in the zinc group. Mean changes in plasma levels of zinc, sIL-1ra, and ICAM-1 differed significantly between groups.
Administration of zinc lozenges was associated with reduced duration and severity of cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc.
Zinc is an essential micronutrient and deficiency is associated with immunoparesis, an increased susceptibility to infections, and slower growth in children. Supplementation reduces the incidence and severity of diarrhoea and lower respiratory tract infections, decreases morbidity and mortality in malaria, and may contribute to improvement in neuropsychological performance and growth. This review examines the potential of zinc to ameliorate HIV disease in children and adults. A summary of the published articles demonstrates that the data is insufficient or flawed to explore this fully. The available data on zinc and immunity suggest that deficiency of the ion may increase HIV replication, impair cellular immunity, and accelerate apoptosis of cells involved in the immune responses. However there is a paucity of data on the effect of zinc supplementation in HIV-infected children. From the available studies in children, it seems that there is no significant deficiency of zinc in HIV infection, no association between zinc levels and disease progression, and little benefit from supplementation. More information is available on zinc and HIV in adults. This shows that the effects of zinc deficiency are inconsistent in seropositive adults, but may include an increase in viral load, lower CD4 numbers, and higher mortality. Zinc supplementation has not been shown to be beneficial in HIV-infected adults or children, and excess zinc supplements may, in fact, be harmful to both children and adults.Accordingly we find that there is no firm evidence that zinc supplementation may be of benefit in improving health or ameliorating disease in HIV-infected children and adults. Well designed trials to test the effects of zinc supplementation in HIV-infected individuals are required; the consequences of zinc deficiency and supplementation on elements of the immune response critical to HIV infection should be examined.
Background: The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment. Objective: Our goal was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status. Design: In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antitubercu-losis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment. Results: At baseline, 64% of patients had a body mass index (in kg/m 2) < 18.5, 32% had plasma retinol concentrations < 0.70 mol/L, and 30% had plasma zinc concentrations < 10.7 mol/L. After antituberculosis treatment, plasma zinc concentrations were not significantly different between groups. Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo (P < 0.05). Sputum conversion (P < 0.05) and resolution of X-ray lesion area (P < 0.01) occurred earlier in the micronutrient group. Conclusion: Vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion. Am J Clin Nutr 2002;75:720–7.
Although known primarily for its antioxidant function, zinc appears to be an important modulator for the production of immune cells as well as ensuring the proper action of various leukocytes such as neutrophils, monocytes, macrophages, B and T lymphocytes. The primary study objective was to compare URI incidence between supplemented (zinc gluconate 15mg/day capsules) and non-supplemented (corn-starch placebo) groups. This study was a seven month randomized, double blind, placebo-controlled trial involving 40 cadets to evaluate zinc's effectiveness in reducing the risk of upper respiratory infections (URIs). Self-reported symptoms as recorded by a weekly web site survey revealed that supplemented participants experienced significantly more symptom free episodes than those in the placebo group (p=0.01). No significant differences were found between groups in terms of physician diagnosed cases (p=0.99). Higher zinc dosage may be warranted to confer a protective effect under more challenging immunological conditions.
Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.
The purpose of this study was to determine the effect of dietary levels of zinc on the immune response of the young adult A/J mouse. Six week old mice were fed ad libitum diets containing adequate (25 jugZn/g), marginal (2.5 jug Zn/g) and deficient (0.5 /¿g Zn/g) levels of zinc. When the mice were immunized with a hapten-carrier antigen on the same day that they were fed the above diets, there was no significant dif ference in the antibody titer among the three groups after 4 weeks even though the thymuses of the zinc déficient mice were markedly atrophied. However in a subsequent experiment, the mice were fed the diets 4 weeks prior to immunization with sheep red blood cells (SRBC). Under these circumstances, the zinc deficient mice produced only 10% and the marginal zinc deficient mice, 25% of the number of anti-SRBC plasmacytes as the control mice. Reconstitution of the zinc deficient mice with thymocytes prior to immunization restored immunity and enabled these mice to pro duce 61% as many anti-SRBC plasmacytes as the control mice. It is con cluded from these experiments that zinc deficiency caused rapid atrophy of the thymus and interfered with T-cell helper function in the young adult mouse but had little effect on the B-cells for the time periods studied. J. Nutr. 107: 1889-1895, 1977.
THE rhinoviruses comprise a subgroup of the picornaviruses, distinguished by their acid lability. They are medically important as the infectious agents of the common cold in man. Although there have been reports of chemical agents which inhibit rhinovirus replication, in only a few instances has the mode of antiviral action been demonstrated at a biochemical level1,2.
Zinc deficiency in humans and animals results in failure to thrive, skin lesions, loss of hair, and diarrhea. The mechanism underlying the diarrhea seen in zinc deficiency is not known. Therefore, the current study was designed to investigate net transport of water, electrolytes, and glucose from segments of small and large intestine in zinc-deficient, pair-fed control, and ad libitum-fed rats. An in vivo single-pass perfusion study was used. The results indicate that net water and sodium transport from the small and large intestine of zinc-deficient rats was significantly decreased compared to corresponding mean values for pair-fed controls and for ad libitum-fed rats. Net absorption of glucose and net secretion of potassium were not significantly different in the three groups. The results are in agreement with previous investigations showing decreased sodium transport in leukocytes and renal tubules of zinc-deficient animals and suggest that zinc may have a role in modulating membrane permeability.
Oral zinc was tried in 15 cases of multibacillary leprosy as an immunostimulant in addition to conventional antileprosy drugs. Results were compared with those in ten similar cases treated with dapsone alone. Cases treated with zinc showed faster clinical improvement, regrowth of eyebrows, rapid fall in the bacterial index (BI) and in the bacterial index in the granuloma (BIG), early and greater influx in lymphocytes in the granuloma, and neovascularization. Upgrading occurred in 6 out of 15 patients taking zinc, but in only 1 out of 10 patients in the control group. Five out of six patients who showed upgrading in the treated group became lepromin positive. Only one patient (BL) showed lepromin conversion in the control group.
Oral zinc sulfate was tried in Eight cases of recurrent Erythema Nodosum Leprosum. To control ENL, they required high dosage of clofazimine and steroids for prolonged periods. After instituting oral zinc, the dose of clofazimine could be reduced to 100 mg twice a week and steroids could be withdrawn completely. Four out of five patients who were not tolerating dapsone earlier, started tolerating dapsone. Incidence and severity of subsequent ENL was also reduced.
Dietary-induced zinc deficiency results in an impaired cell-mediated immune response to non-H2 allogenic tumor cells in mice. Animals maintained on a zinc-deficient diet for as little as 2 weeks develop a severe impairment in their ability to generate a cytotoxic response in the face of tumor challenge. This impairment is totally reversible by returning zinc-deficient mice to normal dietary zinc intake. Such animals now demonstrate a normal cytotoxic response to tumor challenge. If mice are treated with toxic doses of dietary zinc, a similar impairment of the cell-mediated cytotoxic response occurs. This suggests that either a deficiency or toxic level of zinc impairs the immune response to allogeneic tumor cells.
Zinc is perhaps the most important trace element for immune function. Congenital or acquired zinc deficiencies are associated with immune abnormalities and increased susceptibility to infectious diseases. AIDS subjects suffer from reduced zinc bioavailability, more severe in stage IV than in stage III. Such zinc deficiency causes, among other effects, a profound reduction in the biological activity of one of the thymic hormones, thymulin (zinc-facteur-timique-serique, ZnFTS). With these premises, zinc sulphate was administered orally at a daily dose of 200 mg for 30 days to AZT-treated stage III subjects with generalized lymphadenopathy (17 subjects) and stage IV subgroup C1 (12 subjects) AIDS patients. 18 stage III subjects with generalized lymphoadenopathy and 10 stage IV subgroup C1 subjects treated only with AZT served as controls. Zinc sulphate supplementation of stage III and in stage IV C1 patients was followed by an increase or a stabilization in the body weight and an increase of the number of CD4+ cells and the plasma level of active zinc-bound thymulin. The frequency of opportunistic infectious episodes in the 24 months following entry into the study was reduced after zinc supplementation in stage IV C1 subjects (11 infections vs 25 in controls) and delayed in stage III zinc-treated subjects (1 infection/24 months vs 13 infections/24 months in controls). The effect of zinc on opportunistic infections is restricted to infections due to Pneumocystis carinii and Candida, whereas no variations have been observed in the frequencies of cytomegalovirus and toxoplasma infections. These data may support the benefit of zinc as an adjunct to AZT therapy in AIDS pathology.
We have utilized an experimental model of human zinc deficiency for study of cytokines production by TH1 and TH2 cells. Additionally, we determined ratios of CD4+ to CD8+ and CD4+ CD45RA+ to CD4+CD45RO+ cells and percentages of CD73+ T cytolytic cells in the CD8+ subset. The data were collected during baseline, at the end of the zinc-restricted period, and following zinc repletion. Our results showed that functions of TH1 cells, as evidenced by production of interferon-gamma, interleukin-2 (IL-2), and tumor necrosis factor-alpha, were decreased, whereas functions of TH2 cells (production of IL-4, IL-6, and IL-10) were unaffected by zinc deficiency. Thus an imbalance between TH1 and TH2 cells resulted because of zinc deficiency in humans. Our studies also showed that zinc may be required for regeneration of new CD4+ T lymphocytes and maintenance of T cytolytic cells. We conclude that an imbalance between TH1 and TH2 cells, decreased recruitment of T naive cells, and decreased percentage of T cytolytic cells may account for decreased cell-mediated immune functions in zinc-deficient subjects.
Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.
To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori.
Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment.
Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72-100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P < 0.05). On intention-to-treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62-93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86-100%) in the LACP group (P < 0.05).
A 7-day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc.
We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.
Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown.
Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children.
A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques.
Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size: -0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged >6 mo with low initial height-for-age z scores.
Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children.
A syndrome occurring in males, characterized by severe iron deficiency anemia, hypogonadism, dwarfism, hepatosplenomegaly and geophagia, has been observed in villagers in Iran suffering from malnutrition. Eleven such patients, studied in detail, are described.Despite hepatosplenomegaly, results of the liver function tests were uniformly normal except for the serum alkaline phosphatase, which was consistently elevated.The anemia was not associated with blood loss, hookworm infestation or intestinal malabsorption, and responded promptly to oral iron therapy. Although the diet contained adequate amounts of iron it is believed that the predominantly wheat diet, with its high phosphate content, interfered with absorption because of the formation of insoluble iron complexes. Correction of the anemia resulted in marked decrease in the size of the liver and spleen.Prolonged follow-up of patients receiving a well balanced diet indicates that the endocrine abnormalities of growth and sexual development are reversible.The relationship of geophagia (which occurred in nearly all patients) to this syndrome is not clear, and is discussed.The possibility of zinc deficiency is considered as an explanation of hypogonadism, dwarfism and changes in alkaline phosphatase.
To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS).
Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models.
During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89).
The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.
Zinc is an essential micronutrient for human growth, development, and immune function. Zinc deficiency impairs overall immune function and resistance to infection. 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 (18% reduction, 95% CI: 7-28%) and pneumonia (41% reduction, 95% CI: 17-59%), and might lead to a decrease in the incidence of malaria. Zinc has also proven to decrease the duration of diarrhea by 15% (95% CI: 5-24%). Maternal zinc supplementation may lead to a decrease in infant infections. Studies assessing the role of zinc supplementation among persons with HIV, tuberculosis, and the common cold have not been conclusive. Two studies have shown zinc supplementation to decrease child mortality by more than 50%. Zinc clearly has an important role in infant and childhood infectious diseases; programs to increase the intake of zinc among deficient populations are needed.
In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women.
We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women.
Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the ex