To evaluate whether first-trimester zinc status is associated with a reduced incidence of preeclampsia (PE) and improved maternal-neonatal outcomes in pregnant women with chronic hypertension.This retrospective observational study included 205 women with chronic hypertension who were stratified into two groups based on their first-trimester supplementation records: a zinc supplementation group (n = 104, receiving 20mg/day from 12 weeks gestation) and a control group (n = 101, receiving no supplementation). Serum zinc levels, inflammatory markers (TNF-α, hs-CRP), and maternal-neonatal outcomes were assessed and compared between groups.Women in the zinc supplementation group exhibited significantly higher serum zinc levels at 34 weeks (11.64 ± 2.86 vs. 7.85 ± 2.84µmol/L; P < 0.01) and lower levels of TNF-α and hs-CRP (both P < 0.01) compared to the control group. The incidence of PE was significantly lower in the zinc supplementation group (21.15% vs. 38.61%; relative risk [RR] = 0.77, 95% CI [0.63, 0.95], P = 0.01). Furthermore, the zinc group had improved neonatal outcomes, including higher birth weight (2954.52 ± 399.29 vs. 2796.93 ± 474.75g; P = 0.03), a reduced risk of low birth weight (RR = 0.49, P = 0.001), and higher Apgar scores (P = 0.005).First-trimester zinc supplementation is associated with a lower risk of PE and improved neonatal outcomes in women with chronic hypertension. This association may be mediated by anti-inflammatory mechanisms. These findings highlight the potential of zinc-oriented nutritional strategies and warrant further investigation in high-risk pregnancies.

Iron deficiency, with or without anemia, remains a major public health concern among young children in Myanmar. While iron supplementation is widely recommended, its potential adverse effects on growth and gut microbiota warrant investigation, particularly in contexts of poor complementary feeding. To assess the effects of iron supplementation, with or without complementary feeding recommendations (CFRs), on micronutrient status, linear growth and gut microbiota composition among Myanmar children aged 12-23 months, a 24-week randomized controlled trial was conducted in Ayeyarwady Region of Myanmar. Fourteen clusters (villages/wards) were randomized to receive CFRs or not, and children within the clusters were randomized to receive daily aqueous iron or placebo, creating four arms: Placebo (n = 104), CFR (n = 112), Fe (n = 105) and CFRFe (n = 112) totalling 433 children. All intervention groups (CFR, Fe, CFRFe) improved haemoglobin and reduced anaemia risk compared with Placebo (AOR = 0.31 (0.15-0.62), 0.15 (0.07-0.32), 0.14 (0.07-0.31), respectively). CFR and CFRFe also improved zinc status. However, iron-alone (Fe) increased the stunting risk (AOR= 2.74 (1.04-7.23)), while CFRFe did not. No significant effects were observed on gut microbiota composition. Aqueous iron supplementation may impair linear growth when diets are not optimized; combining supplements with optimized complementary feeding may support healthier outcomes. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

Zinc is essential for epithelial integrity and antifungal immunity and may influence host-pathogen interactions in vulvovaginal candidiasis (VVC). However, the relationship between zinc status, zinc-based interventions, and VVC pathogenisis remains unclear. We aimed to assess the clinical efficacy of zinc-based interventions for recurrence prevention and to examine their effects on Candida virulence and inflammatory pathways. We systematically searched the MEDLINE, Scopus, the Cochrane Central Register, and trial registries from inception to September 2025. We included observational, interventional, and experimental studies that evaluated zinc status or zinc-based therapies in VVC. Random-effects meta-analyses were used to estimate the pooled standardized mean differences (SMD) for zinc concentrations with subgroup analyses by sample type and pregnancy status. Risk ratio and risk difference for recurrence outcomes were calculated using Fisher's exact test. Our search identified 45 records and eleven studies (six observational, two randomised controlled trials (RCTs), and three quasi-experimental) met the inclusion criteria. Six plasma/serum comparisons from observational studies were meta-analyzed. Women with VVC had significantly lower systemic zinc levels than controls (pooled SMD = - 0.72, 95% CI: -1.15 to - 0.28, p = 0.001; I²=73.5%). Pregnancy status was a significant moderator (X2 = 9.14, df = 1, p = 0.003), with a much larger effect in pregnant women (SMD - 2.19, 95% CI -3.19 to - 1.18) than in non-pregnant women (SMD - 0.55, 95% CI -0.89 to - 0.21). One RCT (n = 68) showed that zinc supplementation produced a numerically lower 90-day reinfection rate that did not reach statistical significance (28.6% vs. 48.5%, RR = 0.59, 95% CI: 0.31-1.11, p = 0.134). One RCT (n = 192) reported improved pruritus with adjunctive zinc-containing therapy (P < 0.005). Experimental studies demonstrated that zinc restriction upregulates PRA1 expression, enhancing neutrophil-mediated inflammation, while zinc supplementation or zinc oxide nanoparticles downregulate virulence factors (SAP1-3) and attenuate inflammation without reducing fungal burden. Zinc deficiency is associated with VVC, with a larger effect in pregnant women likely reflecting altered zinc physiology in pregnancy. Lower zinc levels in VVC may reflect a host nutritional immunity rather than a pre-existing deficiency, and causality cannot be established from the available cross-sectional evidence. Clinical trials remain insufficient to support zinc-based therapies for routine use in VVC. Not applicable. The protocol was prospectively registered in PROSPERO (CRD420251152091).

Calcium and zinc status and risk of preeclampsia in pregnant women with varying seafood intake in Ambon City: a case-control study.

Background/Objectives: Zinc deficiency has been associated with increased cancer-related mortality, yet its prognostic relevance in patients with breast cancer and comorbid diabetes remains unclear. This study evaluated the association between zinc deficiency and adverse 5-year clinical outcomes in this population. Methods: This retrospective cohort study used the TriNetX database to identify women aged ≥20 years with breast cancer and type 2 diabetes who had recorded serum zinc levels within 3 months before the index date during the period from 1 January 2013 to 4 April 2026. Patients were categorized into zinc-deficiency, normal-zinc, or high-zinc groups. Outcomes included all-cause mortality, hospitalization, intensive care unit admission, and emergency department visits at the 1-, 3-, and 5-year follow-ups. Cox proportional hazards regression models were applied after 1:1 propensity score matching across 12 demographic and clinical variables. Results: Among 648 eligible patients, 282 had zinc deficiency, 311 had normal zinc levels, and 55 had high zinc levels. After matching, 218 remained in each of the zinc-deficient and control groups. Zinc deficiency was associated with higher all-cause mortality at 1 year (hazard ratio [HR], 2.45; 95% CI, 1.41, 4.28), 3 years (hazard ratio [HR], 2.09; 95% CI, 1.34, 3.28), and 5 years (HR, 1.92; 95% CI, 1.27, 2.92), as well as increased risks of emergency department visits, hospitalization, and ICU admission across follow-up periods. No significant differences were observed between the high-zinc and zinc-normal groups, possibly due to limited sample size. Subgroup analyses identified several exploratory subgroup-specific associations. Conclusions: Zinc deficiency was associated with poorer clinical outcomes in women with breast cancer and type 2 diabetes. However, because low serum zinc may also reflect malnutrition, systemic inflammation, frailty, or disease burden, these findings should be interpreted as hypothesis-generating rather than causal.

Associations between polycyclic aromatic hydrocarbon exposure, zinc status, and abnormal lipid profiles in the U.S. population.

Preoperative serum zinc status in morbid obesity patients scheduled for bariatric surgery: A cross-sectional study.

Background and objective. Malnutrition is associated with deficiencies in macronutrients, micronutrients, and trace elements that are necessary for maintaining proper body homeostasis. Protein-energy malnutrition has been linked to low serum zinc and copper levels. The aim of this study was to determine serum zinc and copper levels in malnourished children and to assess their relationship with selected clinical variables. Methodology. A hospital-based case-control study was conducted over a period of 10 months. Forty malnourished patients admitted to Basrah Teaching Hospital were included. Sixty apparently healthy children, matched for age and sex, were selected as a control group. Serum zinc and copper levels were measured in all participants. Results. Severe underweight, wasting, and stunting were recorded in 87.5%, 84.4%, and 78.1% of patients, respectively. Malnourished children had very low mean serum levels of zinc and copper (zinc: 6.32 ± 2.34 µmol/L; copper: 18.45 ± 5.34 µg/dL; p = 0.001). Binary logistic regression analysis showed that age and paternal occupation were independent risk factors for low serum zinc and copper levels (p &lt; 0.05). Conclusion. Mean serum zinc and copper levels were reduced in malnourished children. Parental unemployment and socioeconomic status may be associated with low levels of these trace elements. Further studies are needed to confirm these findings and explore the underlying mechanisms.

Occupational exposures and long-term work-related stressors may accelerate biological aging and contribute to cognitive impairment among high-risk working populations. Zinc (Zn) and copper (Cu) are essential trace elements involved in neurophysiological regulation and may affect cognitive function during aging. However, it remains unclear whether biological age (BA) serves as a potential intermediary factor in the association between Zn and Cu status and mild cognitive impairment (MCI) among occupational populations. This study measured whole blood Zn and Cu levels among coal miners from a large-scale mining facility in northern Shanxi Province, China. Multivariable logistic regression was employed to examine the relationship of Zn and Cu concentrations with MCI. Potential dose-response patterns and non-linear trends were further evaluated using restricted cubic spline (RCS) functions. Constructed the BA to reflect the physiological status of coal miners by integrating multiple biochemical and functional indicators. In addition, mediation analyses were performed to quantify the indirect association of BA within these relationships. Participants with moderate whole blood Zn levels exhibited a reduced likelihood of MCI (OR = 0.51, 95% CI: 0.31–0.86), whereas the association attenuated at higher concentrations. RCS analysis suggested a U-shaped pattern, with the lowest MCI risk observed at intermediate Zn levels. BA statistically explained 28.53% of the association between Zn and MCI in cross-sectional mediation analysis. Whole blood Cu levels did not show a significant relationship with the risk of MCI. These findings suggest a non-linear association between Zn status and cognitive health in occupational populations, with potential involvement of aging-related processes reflected by BA. Incorporating aging-related indicators into occupational health assessment may help identify workers at elevated risk of cognitive impairment.

Background: The chronic inflammatory bowel illness known as ulcerative colitis (UC) is characterized by dysregulated mucosal immunity. There is much more to learn about the relationship between interleukin-17 (IL-17), a key mediator in the Th17 pathway, and systemic inflammatory and metabolic indicators. Objectives: To examine the relationship between inflammatory (CRP), metabolic (FBS, HbA1c), and micronutrient (zinc) indicators and blood levels of IL-17 in individuals with UC, while excluding those with diabetes, autoimmune, hepatic, or renal disorders. Methods: In a case-control research, 90 participants were matched for age, sex, and BMI: 45 UC patients and 45 healthy controls. Measurements were made of zinc, HbA1c, FBS, CRP, and serum IL-17. Using Pearson correlation and independent t-tests, the data were examined. Results: IL-17 levels in UC patients were substantially greater than those in controls (63.85 ± 6.53 vs. 28.38 ± 4.94 pg/mL, p = 0.01). Moreover, CRP was significantly higher (31.29 ± 5.42 vs. 2.64 ± 0.28 mg/L, p = 0.01). IL-17 and CRP showed a high positive association in the UC group (r = 0.804, p < 0.01). On the other hand, zinc levels in UC patients were considerably lower (55.82 ± 3.32 vs. 89.18 ± 5.36 μg/dL, p = 0.001). The groups' FBS and HbA1c levels did not vary significantly from one another. Conclusion: Increased systemic release of IL-17 along with its robust positive association with CRP suggest a key role of IL-17 in active systemic and mucosal inflammation in UC, whereas low levels of zinc contribute to exaggerated Th17 responses. Importantly, these findings were robust even after excluding the patients who were both autoimmune positive and who had metabolic and systemic autoimmune comorbidities which also increased the reliability of these findings. In UC, zinc status in relation to IL-17 may be a focus for diagnosis and treatment.

Malaria remains a major cause of morbidity and anaemia in endemic regions, disproportionately affecting young children and pregnant women. Zinc, an essential micronutrient that supports immune regulation and erythropoiesis, has been investigated as a potential adjunctive intervention to mitigate malaria and its haematological consequences. This systematic review synthesized evidence from randomized controlled trials, observational studies, and mechanistic investigations published between 2013 and 2025 to clarify zinc’s effects on malaria incidence, parasitemia, and anaemia-related outcomes. Comprehensive searches were conducted across Medline, Embase, Web of Science, Scopus, Cochrane Central, and Global Health, supplemented with grey literature from ClinicalTrials.gov and WHO ICTRP. Eligible studies included zinc supplementation trials, epidemiological analyses of zinc status, and mechanistic studies of zinc-dependent pathways, with methodological quality assessed using RoB 2, ROBINS-I, and GRADE frameworks. The findings indicated that zinc-only supplementation did not significantly reduce malaria incidence or parasitemia; however, multi-micronutrient interventions containing zinc showed modest improvements in malaria outcomes and greater effects on anaemia recovery. Zinc consistently enhanced hemoglobin levels and reduced anaemia severity among high-risk groups, even when parasitological outcomes remained unchanged. Mechanistic evidence attributed these effects to zinc’s regulatory roles in immune modulation, hepcidin control, and erythropoiesis, while also identifying parasite zinc-binding proteins as potential therapeutic targets. Study heterogeneity was influenced by baseline zinc deficiency, malaria transmission intensity, pregnancy status, and socioeconomic factors. Overall, zinc supplementation should not be regarded as a standalone antimalarial intervention but rather as an essential adjunct within integrated nutrition and malaria-control strategies.

Interaction of serum zinc and copper status with fatty acid desaturases on incidence of type 2 diabetes in the EPIC-Potsdam study.

Children living in resource-limited regions with inadequate environmental sanitation, such as the Bolivian highlands, are affected by parasitic infections that may compromise nutritional status. Objective: This study aimed to assess the prevalence of intestinal parasitic infections and their associations with nutritional status, micronutrient deficiencies, and anemia in school-aged children from La Paz, Bolivia. Methods: A cross-sectional study was conducted among 212 schoolchildren aged 5-13 years in the municipality of La Paz, in highland areas characterized by high poverty levels. Parasitological examination, anthropometric measurements, and biochemical assessment of micronutrients (vitamins A and D, zinc, iron) were performed to evaluate children's health status. Results: Mild malnutrition was more prevalent than moderate-to-severe forms. Micronutrient analysis revealed substantial deficiencies in vitamin A (39%), zinc (25%), and vitamin D (18%). Zinc deficiency was significantly more common in children aged 11-13 years compared to younger age groups (p = 0.034). Intestinal protozoan infections showed significant associations with micronutrient deficiencies. Giardia lamblia infection was associated with both vitamin A (30.9%, p = 0.042) and vitamin D (78.9%, p = 0.001) deficiencies. Blastocystis spp. infection was similarly linked to higher prevalence of vitamin A (35.8%, p = 0.025) and vitamin D (69.7%, p = 0.004) deficiencies. Entamoeba coli infection was significantly associated with vitamin D deficiency (p = 0.021), while Iodamoeba bütschlii infection showed a significant association with zinc status (p = 0.027), with notably lower zinc deficiency prevalence in infected children (7.7%) compared to non-infected children. Among helminth infections, Ascaris lumbricoides was significantly associated with vitamin D deficiency (37%, p = 0.018). Moderate-to-severe anemia was highly prevalent, affecting over half of the children regardless of sex. Wasting (BAZ) was significantly associated with age (p = 0.030), with moderate-to-severe cases most prevalent in children aged 5-7 years and absent in older groups, while mild wasting increased with age. In univariate logistic regression analysis, zinc deficiency emerged as a significant risk factor for anemia (OR = 2.51, 95% CI: 1.19-5.29, p = 0.016). No significant associations were observed between anemia and sex, age group, vitamin A or D status, or anthropometric indicators including underweight, stunting, or wasting. Conclusions: These findings highlight the substantial burden of micronutrient deficiencies, parasitic infections, and anemia among children in this impoverished region, underscoring the urgent need for targeted public health interventions addressing nutritional supplementation, parasite control, and improved sanitation.

Background: Hypothyroidism is a common endocrine disorder with significant metabolic consequences. Apart from iodine, trace elements such as zinc (Zn) and copper (Cu) play an essential role in thyroid hormone synthesis, metabolism, and action. Alterations in these micronutrients may contribute to the pathophysiology of hypothyroidism. Aim: To evaluate serum zinc and copper levels in patients with hypothyroidism and compare them with euthyroid healthy controls, and to assess their association with thyroid hormone levels. Materials and Methods: This hospital-based case–control study included 100 subjects aged 18–65 years. Fifty patients with biochemically confirmed hypothyroidism constituted the case group, while fifty age- and sexmatched euthyroid individuals served as controls. Serum T3, T4, and TSH were estimated by chemiluminescence immunoassay. Serum zinc and copper levels were measured using spectrophotometric methods. Statistical analysis was performed using Student’s t-test and correlation analysis. Results: Mean serum zinc levels were significantly lower in hypothyroid patients compared to controls (32.3 ± 19.1 vs 86.0 ± 17.9 µg/dL; p &lt; 0.001). Serum copper levels showed no statistically significant difference between cases and controls (p &gt; 0.05). Serum zinc demonstrated a significant negative correlation with TSH and a positive correlation with T3 and T4 levels. Conclusion: Hypothyroidism is associated with significantly reduced serum zinc levels, while serum copper levels remain largely unchanged. Zinc deficiency may play an important contributory role in thyroid dysfunction and may warrant attention during clinical evaluation of hypothyroid patients.

Background: Liver cirrhosis is a major global health problem, often accompanied by micronutrient deficiencies, particularly zinc, which is essential for hepatic metabolism, immune function, and ammonia detoxification. Data on serum zinc levels and associated factors in Bangladeshi patients are limited. This study aimed to assess zinc status and its clinical associations in cirrhotic patients at a tertiary hospital. Methods: A cross-sectional analytical study was conducted from July 2024 to June 2025 at Dhaka Medical College Hospital. Fifty-five patients aged 18–70 years with clinically diagnosed liver cirrhosis were enrolled. Data were collected through a structured questionnaire, and serum zinc levels were measured from blood samples using standard laboratory methods. Statistical analysis was performed using SPSS version 26, with p &lt; 0.05 considered significant. Ethical approval and informed consent were obtained. Results: Of the 55 participants, 67% were male, with a mean age of 46 ± 12 years. Compensated and decompensated cirrhosis were nearly equally represented (49.1% vs. 50.9%). HBV was the predominant etiology (75%), with HCV accounting for 25%. Decompensated patients had higher prevalence of diabetes (71% vs. 37%), hypertension (82% vs. 56%), and chronic kidney disease (89% vs. 33%), whereas ischemic heart disease was similar across groups. Serum zinc levels were significantly lower in decompensated patients (0.41 ± 0.14 mg/L) than compensated patients (0.64 ± 0.20 mg/L). Overall, 65% of patients were zinc deficient, and deficiency was significantly associated with hypertension and chronic kidney disease. Conclusion: Zinc deficiency is highly prevalent in cirrhosis and correlates with disease severity and comorbidities. Monitoring and correcting zinc levels may provide prognostic information and guide therapeutic strategies, particularly in decompensated cirrhosis. DOI: https://doi.org/10.52783/jchr.v16.i1.12012

Background/Objectives: Zinc is an essential trace element involved in multiple aspects of immune function, including epithelial barrier integrity, innate and adaptive immune responses, regulation of inflammation and oxidative stress. Zinc deficiency has been associated with increased susceptibility to infections, particularly in the pediatric population. This narrative review aims to summarize and discuss current evidence on the role of zinc in the prevention and management of pediatric respiratory infections. Methods: A comprehensive literature review was conducted including randomized controlled trials, real-world studies, and international guidelines published in recent years. Both zinc monotherapy and multicomponent dietary supplements containing zinc were considered. Results: Evidence consistently supports a preventive role of zinc supplementation in reducing the incidence and burden of respiratory infections, particularly in children with recurrent disease and in zinc-deficient populations. Zinc-containing multicomponent supplements demonstrated significant reductions in infection frequency and duration, alongside improved patient and parent-reported outcomes, with a favorable safety profile. In contrast, data on zinc as an adjunctive treatment during acute infections, especially severe pneumonia, are less consistent, with limited impact on major clinical outcomes. The effectiveness of zinc appears to be influenced by treatment duration, baseline nutritional status, and formulation. Conclusions: In conclusion, zinc may represent a valuable component of preventive immune-nutritional strategies for pediatric respiratory infections, especially when administered as part of multicomponent formulations and over prolonged periods. While its role in acute disease management remains uncertain, optimizing zinc status may contribute to reducing infection recurrence and overall disease burden. Further well-designed trials are warranted to clarify optimal dosing, timing, and target populations.

Background: AMP-activated protein kinase (AMPK) acts as a key energy sensor that negatively regulates skeletal muscle mass. Zinc is an essential trace element that is required for myogenic differentiation and protein synthesis, while zinc deficiency has been associated with muscle atrophy in vivo. However, how zinc status modulates AMPK activation itself or alters downstream responses to AMPK signaling in muscle cells remains unclear. Methods: C2C12 myotubes were cultured under zinc-depleted (ZnD), zinc-sufficient (20 μM; Zn20), or zinc-supplemented (40 μM; Zn40) conditions. AMPK was activated by AICAR, and zinc status-dependent responses were evaluated using molecular and morphological analyses. Results: AICAR increased intracellular zinc levels in Zn20 and Zn40 but not in ZnD. Zinc transporter expression exhibited gene-specific regulation: Zip3 was upregulated across all zinc conditions, Zip14 was significantly induced in ZnD and Zn40, and Zip10 was selectively upregulated in Zn40. AICAR induced myotube atrophy in all groups; however, the reduction in myotube diameter was significantly greater under zinc-depleted conditions. Zinc depletion was associated with transcriptional upregulation of FoxO1, FoxO3, Atrogin-1, and MuRF1 in response to AICAR, while AMPK activation and suppression of S6K1 phosphorylation occurred to a similar extent regardless of zinc status. Conclusions: These findings indicate that zinc availability does not alter AMPK activation itself but modulates downstream atrophic responses to AMPK signaling. Under conditions of AMPK activation, adequate zinc availability is accompanied by increased intracellular zinc levels and stress-responsive ZIP regulation, which may limit excessive atrophic gene induction, whereas zinc depletion increases susceptibility to AMPK-induced atrophic responses in skeletal muscle cells.

Zinc is an essential trace element with antioxidant and signaling functions critical to cardiac physiology. This study investigated the role of zinc in myocardial ischemia-reperfusion (IR)-induced cardiac damage using a rat model, and whether zinc deficiency induced by intermittent hypoxia (IH) exacerbates cardiac injury. Regional IR was performed in isolated rat hearts, and zinc concentrations were measured in coronary effluents. Plasma zinc status was assessed following 14- or 35-day IH exposure (1-min cycles alternating 21% and 5% FiO₂, 8h/day). The cardioprotective effects of intracoronary zinc administration with the ionophore pyrithione were evaluated based on arrhythmias, infarct size, and contractile recovery. Myocardial IR induced significant zinc release upon reperfusion (615.7±78.2nM vs. 374.5±40.3nM pre-reperfusion, P<0.01). Zinc administration during reperfusion reduced arrhythmia duration (358.0±61.7sec vs. 559.9±31.6sec, P<0.01) and improved myocardial recovery. IH exposure led to reduced plasma zinc levels (10.3±0.5 µM vs. 13.0±1.2 µM, P=0.057) and significantly increased infarct size following IR (43.9±4.2%vs. 29.2±4.3%, P<0.05). Zinc-pyrithione treatment during reperfusion abolished the deleterious effects of IH on infarct size. IH-induced zinc deficiency exacerbates cardiac vulnerability to IR injury, while zinc restoration through targeted administration mitigates this damage. Zinc's protective effects may involve antioxidant action, calcium homeostasis, and signaling modulation. Zinc plays a critical role in limiting IR-induced cardiac damage. Zinc supplementation during reperfusion may offer therapeutic benefit, particularly in conditions associated with chronic IH, such as obstructive sleep apnea.

Zinc is an essential micronutrient involved in structural, catalytic, and regulatory functions across all levels of biological organization. Despite substantial advances over the past two decades, the zinc literature remains highly fragmented, with mechanistic, nutritional, and clinical findings often reported in isolation. Additionally, the synergistic interactions between zinc and other micronutrients-particularly minerals and vitamins-are dispersed across multiple research domains, complicating efforts to understand their integrated roles in maintaining homeostasis. Recent developments in artificial intelligence (AI) present new opportunities to consolidate these data, enabling multi-scale analyses of zinc-dependent processes and the broader zinc interactome. Although a complete map of the zinc interactome is not yet feasible, an integrative perspective is needed to contextualize zinc's contributions within the framework of the hallmarks of health. This narrative review highlights zinc's involvement in cellular maintenance, metabolic regulation, stress response, and systemic physiological function. It further examines how disruptions in zinc status, alone or in combination with other nutrient imbalances, contribute to clinically relevant disorders. By combining current knowledge across molecular, cellular, and systems biology levels, this review illustrates zinc's pleiotropic effects on physiological resilience and healthspan, with particular emphasis on its role in nutritional status, homeostatic regulation, and overall human health.

Aging impacts immunity, zinc status, and overall health, with these factors being closely interconnected. Zinc is known to modulate protein expression and cytokine production, with new molecular mechanisms continuing to be identified. ZIP8 facilitates IFN-γ production by increasing the intracellular zinc levels; how zinc status in humans affects ZIP8 expression remains unclear. We assessed serum zinc, dietary zinc intake, proton pump inhibitor (PPI) use, phytohemagglutinin (PHA)-stimulated IFN-γ production, and ZIP8 protein expression in elderly hospitalized patients and young healthy controls. Compared to young adults, elderly participants exhibited lower zinc status and IFN-γ levels, with PPI use among the elderly correlating with zinc deficiency. Zinc-deficient elderly participants received zinc aspartate supplementation for approximately 7 days, resulting in increased serum zinc levels, IFN-γ production, and a trend toward increased ZIP8 expression; in participants taking PPIs, this increase reached statistical significance. Although we found no clear correlation between ZIP8 expression and zinc status, the observed response to supplementation warrants further investigation. These findings reinforce the relevance of zinc supplementation in the elderly, although further studies are needed to elucidate the precise mechanisms linking zinc status to IFN-γ production, particularly regarding the role of ZIP8 expression levels.