Plasma Zinc Concentrations Research Articles

Low thiamine status in adults following low-carbohydrate / ketogenic diets: a cross-sectional comparative study of micronutrient intake and status.

Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs. A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD (n = 49) or diets not restricting carbohydrates (controls; n = 49). Diets were assessed using the 130-item EPIC-Norfolk food-frequency questionnaire. Red-blood-cell thiamine diphosphate (TDP) was measured for thiamine status using HPLC. Plasma magnesium, zinc, copper, and selenium were measured using inductively coupled plasma mass spectrometry. Between-group biomarker comparisons were conducted using ANCOVA and adjusted for age, sex, body mass index (BMI), and diabetes status. LCD-followers (26% male, median age 36 years, median BMI 24.2 kg/m2) reported adhering to LCDs for a median duration of 9 months (IQR 4-36). The most followed LCD type was 'their own variations of LCD' (30%), followed by ketogenic (23%), 'palaeolithic' (15%), and Atkins diets (8%). Among controls, 41% were male (median age 27 years, median BMI 23kg/m2). Median macronutrient intakes for LCD vs control groups were carbohydrate 16%Energy (E) vs. 50%E; protein 25%E vs. 19%E; and fat 55%E vs 34%E (saturated fat 18%E vs. 11%E). Two-thirds of LCD followers (32/49) and half of the controls (24/49) reported some use of dietary supplements (p = 0.19). Among LCD-followers, assessing from food data only, 21 (43%) failed to meet the reference nutrient intake (RNI) for thiamine (vs.14% controls, p = 0.002). When thiamine from supplementation (single- or multivitamin) was included, there appeared to be no difference in thiamine intake between groups. Still, red-blood-cell TDP was lower in LCD-followers than controls (407 ± 91 vs. 633 ± 234 ng/gHb, p < 0.001). Three LCD-followers were thiamine-deficient (RBC thiamine < 275 ng/gHb) vs. one control. There were no significant differences in dietary intakes or plasma concentrations of magnesium, zinc, copper, and selenium between groups. Following LCDs is associated with lower thiamine intake and TDP status than diets without carbohydrate restriction, incompletely corrected by supplement use. These data, coupled with a lack of RCT evidence on body weight control, do not support recommending LCDs for weight management without appropriate guidance and diet supplementation.

Plasma Zinc Levels in Patients with Diabetic Nephropathy: Is there a Relationship with NLRP3 Inflammasome Activation and Renal Prognosis?

Zinc is an essential trace element, and impaired zinc homeostasis may be associated with inflammation in patients with diabetic nephropathy (DN). We investigated the influence of zinc level on nod-like receptor nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome expression and renal prognosis in patients with DN. We recruited 90 patients definitively diagnosed with DN by renal biopsy and 40 healthy controls. Zinc, NLRP3, interleukin (IL)-1β, and IL-18 levels were detected in blood samples, and the correlations between these parameters were assessed. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) evaluated the predictive value of zinc and the NLRP3 inflammasome for DN. Furthermore, patients with DN were divided into low- and normal-zinc groups to observe differences in clinical indicators and identify expression of inflammatory-related factors in renal tissue. Kaplan-Meier survival curves predicted the impact of zinc levels on renal prognosis. We found thatthe plasma zinc concentration in patients with DN was lower, while NLRP3, IL-1β, and IL-18 levels were higher than were those in patients without DN (P < 0.05). Zinc level was negatively correlated with NLRP3, IL-1β, and IL-18 levels (P < 0.01). Zinc and the NLRP3 inflammasome were predictive of DN, but their combination improved the diagnostic value. The DCA curve demonstrated a good positive net benefit in the combined model. Compared to patients with low zinc levels, patients with normal zinc levels had lower expression of NLRP3 inflammasome and a better prognosis. Zinc has a protective effect on DN and may affect NLRP3 inflammasome activation.

Metabolomic changes in tear fluid following zinc biofortification in the BiZiFED nutritional study: a feasibility study.

Biofortified Zinc Flour to Eliminate Deficiency in Pakistan (BiZiFED) is a nutritional research program that evaluates the impact of consuming zinc biofortified wheat flour on zinc status and associated health outcomes of vulnerable communities in northwest Pakistan. Measuring zinc status from blood samples is fraught with problems. This feasibility study evaluated whether metabolite changes in tear biofluids could be used to understand zinc status. Zinc deficiency is particularly prevalent amongst the female population in Pakistan. Therefore, a crossover trial was developed in which 25 women of reproductive age received standard, wheat flour, and another 25 received zinc-biofortified wheat flour for 8 weeks. At the end of this period, the nutritional intervention was switched between the groups for another 8 weeks. Tear biofluid was collected using Schirmer strips at baseline and after 8 and 16 weeks. Metabolomic analysis was conducted using the MxP® Quant 500 kit on the tear biofluid from a subset of the study participants. Two metabolites had a significantly negative correlation with plasma zinc concentration: tiglylcarnitine and valine. Compared to baseline metabolite concentrations, acetylcarnitine, glutamine, two lysophosphatidylcholines (lysoPC a C16:0 and lysoPC a C18:1), and four sphingomyelins (SM (OH) C16:1, SM C16:0, SM C16:1, and SM C24:0) were all significantly decreased post-zinc intervention, whilst a ceramide (Cer(d18:1/18:0) was significantly increased. These results highlight the potential of using tear biofluids as an alternative source for metabolomic biomarkers, both for the assessment of the zinc status of individuals enrolled in nutritional studies and for indicating physiological changes that arise from nutritional supplementation.

Association of seminal plasma zinc levels with human semen quality and its toxic effects on sperm motility

Infertility has become one of the most common chronic diseases among reproductive- aged individuals, and male factors account for about 50 %. Zinc is a trace element that is essential for sperm quality and male reproductive system. Although several current studies with small sample sizes have investigated this relationship, the conclusions have been still controversial. Here, using a large population sample involved 25,915 participants from Changzhou Maternity and Child Health Care Hospital, we revealed an inverted “U”-shaped trend between seminal plasma zinc concentrations and sperm motility PR/PR + NP (PR, progressive motility; NP, non-progressive motility). The results showed that the highest values of sperm PR/PR + NP observed in the group with intermediate concentrations of zinc (Group 2, 0.25–2.11 mmol/L). The mean values were 43.17 ± 19.03 % and 56.64 ± 20.28 %, respectively. And the lowest values came out in the highest zinc levels group (Group 4, > 3.04 mmol/L). In vitro cell experiments also showed that zinc caused dose-dependent cytotoxicity for GC-2 cells at a threshold value. Furthermore, RNA-seq analysis demonstrated that high concentrations of zinc exerted toxic effects on GC-2 cells through immune injury. Taken together, our findings suggested that moderate amounts of zinc are crucial for human reproduction and excessive concentrations may have adverse effects on male fertility.

Plasma, Urinary, Erythrocyte and Platelet Zinc Concentrations in Soccer Players.

Essential trace minerals are vital for general human health and athletic performance. Zinc (Zn) plays critical roles in several biochemical processes in exercise physiology, especially during intense physical exercise. This research aimed to analyze erythrocyte, platelet, plasma and urine Zn concentrations among men's and female soccer players over a sports season. A total of 22 male soccer players (20.61 ± 2.66 years; 71.50 ± 5.93 kg) and 24 female soccer players (23.37 ± 3.95 years; 59.58 ± 7.17 kg) participated in this longitudinal quasi-experimental study. Three assessments were carried out over the season: 1st evaluation: first week of training (August); 2nd assessment: middle of the season, between the end of the first and second round (January) and 3rd assessment: last week of training (May/June). In all evaluations extracellular (plasma and urine) and intracellular (erythrocytes and platelets) Zn concentrations were determined, as well as physical fitness and several blood parameters. Inductively coupled plasma mass spectrometry was used to measure Zn concentrations. Plasma and urinary concentrations were higher among male soccer players (p < 0.05) while erythrocyte and platelet Zn concentrations were higher in the female soccer players (p < 0.05). Additionally, variations in urinary and platelet Zn concentrations were observed over the season. The differences could be related to muscle mass, muscle damage or the specific sport's physical demands.

Effect of Zinc and Vitamin E on Blood Testosterone and Inflammatory Markers in Male Patients Undergoing Heart Surgery

Background: Zinc and vitamin E affect the metabolism of testosterone and inflammatory factors. We aimed to evaluate the effect of zinc and vitamin E supplementation on plasma testosterone levels and inflammatory markers in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: This study was a secondary analysis of a previously published randomized controlled trial in a subsample of male patients undergoing CABG surgery. Patients in the zinc-vitamin E group (n = 27) received oral zinc (120 mg) and vitamin E (1200 international units) one day prior to surgery, followed by 30 mg of zinc and 200 units of vitamin E per day for three weeks after surgery. Patients in the control group (n = 25) received a placebo. Plasma levels of total testosterone, cortisol, interleukin-6 (IL-6), and white blood cell toll-like receptor-4 (TLR-4) gene expression were determined at three-day and three-week intervals following surgery. Changes in these markers were analyzed using a repeated-measures analysis of variance. Results: A comparison of the groups revealed no significant difference in the concentration of plasma total testosterone levels (P = 0.059) or cortisol. Three weeks following the surgical procedure, a positive correlation was observed between the change in plasma zinc concentrations and the change in plasma testosterone levels (r = 0.32; P = 0.025). The administration of zinc and vitamin E supplements resulted in a reduction in plasma IL-6 levels on postoperative day 3 (P = 0.025), while no significant effect was observed in week 3 (P = 0.091). The expression of the TLR-4 gene in WBCs was found to be lower in the zinc-vitamin E group compared to the placebo group on day 3 (P = 0.051) and week 3 (P = 0.025). Conclusions: The administration of zinc and vitamin E to patients undergoing CABG was associated with a relative improvement in postoperative inflammatory markers. Plasma zinc levels demonstrated a correlation with testosterone levels, suggesting a potential avenue for further research in these patients.

Analysis of transition metals in glioblastoma tumor and plasma samples.

e14029 Background: Transition metals such as copper, iron, zinc, and manganese are known to play essential roles in human physiology as evidenced in conditions where these metals are dysregulated. The role of transition metals in glioblastoma biology has been largely understudied. Here we investigated whether plasma and tumor transition metal content is associated with glioblastoma patient outcomes. Methods: Transition metal content was measured in 31 glioblastoma tumor samples, 21 of which had matched plasma samples, using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES). Concentrations of transition metals in plasma and tumor were then then correlated with clinical parameters including median overall survival (mOS) as well as plasma cytokines. Results: Spearman correlation analysis of transition metals in glioblastoma tumor samples found that tumor manganese and tumor zinc (R = 0.52, p = 0.0048) as well as tumor copper and tumor zinc (R = 0.36, p = 0.038) were positively correlated. Plasma transition metal content did not correlate with tumor transition metal content. Kaplan-Meier and Cox regression survival analysis between high and low expressors of each respective transition metal, separated at the median, revealed that high plasma iron content was associated with prolonged survival (median overall survival: 30.1 vs 12.4 months, P = 0.0036). Plasma from glioblastoma patients in the high plasma iron group had increased levels of IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004). Plasma or tumor concentrations of copper, zinc, or manganese did not associate with survival. Conclusions: Increased plasma iron content is associated with prolonged survival as well as increased plasma IFN-β levels, suggesting a possible link between iron and immune responses in glioblastoma patients.

Associations between plasma metal elements and risk of cognitive impairment among Chinese older adults.

The relationship between plasma metal elements and cognitive function is unclear, especially in extremely older individuals. This present study aimed to explore the association between plasma metal concentrations and the risk of cognitive impairment (CI) in Chinese extremely older adults. Individuals aged ≥90 years with plasm metal concentration data from the fifth wave of the 2008 Chinese Longitudinal Healthy Longevity Survey were included. Plasma selenium (Se), manganese (Mn), magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), and zinc (Zn) concentrations were measured using inductively coupled plasma optical emission spectroscopy. Cognitive function was assessed by the Chinese version of the mini-mental state examination. The study enrolled 408 participants. Participants with CI had significantly lower plasma Se, Mn, and Fe levels and higher Ca levels than those with normal cognitive function (p < 0.05). Plasma Se, Mn, Ca, and Fe concentrations were significantly associated with CI risk in both single- and multiple-element logistic regression models. Additionally, the multiple-element model results showed that the adjusted odds ratios for CI were 0.042 (95% confidence interval 0.016-0.109), 0.106 (0.044-0.255), 7.629 (3.211-18.124) and 0.092 (0.036-0.233) for the highest quartiles compared to the lowest quartiles of Se, Mn, Ca, and Fe, respectively. Moreover, subgroup analyses by age, sex, and body mass index suggested a consistent significant correlation (p < 0.05). Therefore, decreased plasma Se, Mn, and Fe and increased plasma Ca levels were associated with CI risk in Chinese older adults. These findings are of great significance for the development of programs to delay cognitive decline in the elderly.

Plasma and red blood cell concentrations of zinc, copper, selenium and magnesium in the first week of paediatric critical illness

Critically ill children are at risk of micronutrient deficiencies, which might lead to poor clinical outcomes. However, the interpretation of micronutrient concentrations in plasma is complicated due to age-dependent and critical illness-dependent changes. Certain red blood cell (RBC) concentrations might reflect the overall body status more reliably than plasma levels in the presence of systemic inflammatory response. This study longitudinally examined micronutrient concentrations in both plasma and RBC in critically ill children. This secondary analysis of the PEPaNIC RCT investigated the impact of early versus late initiation of parenteral macronutrient supplementation in critically ill children. All children received micronutrients when EN was insufficient (<80% energy requirements). Blood samples were obtained on days 1, 3, 5 and 7 of Paediatric Intensive Care Unit (PICU) admission. Inductively coupled plasma mass spectrometry was used to measure zinc, selenium, and copper in plasma and selenium, copper, and magnesium in RBCs. Plasma magnesium was measured with colorimetric detection. Micronutrient concentrations were compared with age-specific reference values in healthy children and expressed using Z-scores. Changes in micronutrient concentrations over time were examined using the Friedman and post hoc Wilcoxon signed-rank tests. For 67 critically ill children, median (Q1; Q3) age 9.5 (5.5; 13.2) years, PIM3 score-2.3 (-3.1;-0.8), samples were available at various time points during their PICU stay. For 22 patients, longitudinal samples were available. On day 1, the median plasma Z-score for zinc was-5.2 (-5.2;-2.9), copper-1.6 (-2.9;-0.2), selenium-2.6 (-3.8;-1.0), magnesium-0.2 (-1.6; 1.3), and median RBC Z-score for copper was 0.5 (-0.1; 1.3), selenium-0.3 (-1.1; 0.7), magnesium 0.2 (-0.4; 1.3). In the longitudinal analysis, plasma zinc was significantly higher on day 5 (Z-score-3.2 (-4.6;-1.4)) than on day 1 (Z-score-5.2 (-5.2;-3.0), p=0.032), and plasma magnesium was significantly higher on day 3 (Z-score 1.1 (-0.7; 4.0)) than on day 1 (Z-score-0.3 (-1.6; 0.5), p=0.018). Plasma copper and selenium remained stable, and the RBC concentrations of all micronutrients remained stable during the first five days. Most patients had low plasma zinc, copper and selenium concentrations in the first week of their PICU stay, whereas they had normal to high RBC concentrations. More research is needed to examine the relationships between micronutrients and clinical outcome.

Detection of Trace Elements Se, Cu, and Zn Levels in Biological Samples of Drug Abusers: Halani Sindh, Pakistan.

Illicit drug use has become a global issue, posing significant health, socioeconomic, and cultural risks. The study examined essential trace metals: selenium, zinc, and copper in blood concentrations, as well as in serum and scalp hair samples, from 240 male drug-abuse subjects/patients aged 18-45, categorized into three age groups. The study compared 45 healthy subjects of the same age group using an acid digestion method supported by a microwave oven during sample preparation. The technique of atomic absorption spectrometry was employed to identify essential and toxic elements, utilizing certified reference materials for accuracy. According to a recent study, plasma zinc and selenium concentrations in drug abusers are lower than those in referent subjects, potentially increasing vulnerability to infection due to poor nutritional status or other contaminants.

Zinc – a scoping review for Nordic Nutrition Recommendations 2023

Zinc is essential for several biological processes including those critical for the immune system, DNA synthesis, cell division, and growth. Zinc is involved in the pathophysiology of chronic diseases and protects proteins and lipids from oxidative damage. Inadequate zinc intake and low plasma zinc concentration are associated to an increased risk of chronic diseases such as cardiovascular diseases and type 2 diabetes; however, the evidence is limited. Zinc deficiency increases the risk of infections and poor growth and may contribute to the high burden of infectious diseases and stunting in children living in low- and middle-income countries. The risk of zinc deficiency in the populations of the Nordic and Baltic countries is low.

Hemoglobin Response to Zinc Supplementation in Chronic Kidney Disease in Patients with Zinc Deficiency and Anemia

Background: Chronic anemia has an estimated prevalence of 5.6% within the US, where 25.3% of patients with chronic kidney disease (CKD) 3-5 have anemia of chronic kidney disease according to NHANES. Anemia in CKD has long been attributed to a decrease in EPO production due to their kidney disease. While iron deficiency is treated in anemia of chronic kidney disease, other micronutrients are less commonly tested or supplemented. Zinc may be an additional micronutrient of interest in anemia of chronic kidney disease as zinc has numerous proposed mechanisms in erythropoeisis including acting as a catalyst in the iron metabolism and heme synthesis through the activity of alpha-aminolevulinic acid dehydratase enzyme. Zinc is found in the structure of the growth factor independent 1B (Gfi-1B) Zinc finger protein and GATA-1 Zinz finger transcription factor, which functions as a regulator in erythroid cell growth by modulating gene expression specific to erythroid series including the SMAD pathways and TGF-β signaling. The interaction with zinc in signaling cascades such as the growth hormone and insulin-like growth factor-1 pathways also result in increased erythropoietin transcription and therefore increased erythropoiesis. In addition, zinc is regarded as an important erythroid differentiation factor which progress maturation of erythrocytes. Zinc has also shown to stimulate EPO production in nephrectomized rats and Zinc supplementation increased reticulocyte production in human subjects. This descriptive, retrospective study describes zinc deficient patients with CKD 3-5 and chronic anemia; who underwent oral zinc supplementation, and their changes in hemoglobin (HGB) over a 12 month period in an academic outpatient hematology clinic in California, United States of America. Objectives: Primary endpoints: determine the rate of anemia resolution over 12 months following supplementation of zinc in patients with zinc deficiency, CKD, and anemia of chronic kidney disease. Secondary endpoints: determine if zinc supplementation in zinc deficient patients with chronic anemia and CKD 3-5 will improve HGB by at least 1.0 g.dL by 1, 3, 6, and 12 month time points. Methods: Hematology patients from Loma Linda University Cancer Center over the age of 18 who had CKD 3 or above (GFR &amp;lt;59 ml/min) with chronic anemia (HGB &amp;lt;12 for women, HGB &amp;lt;13 for men for &amp;gt;3 months) were identified to have zinc deficiency (plasma zinc concentration &amp;lt;65 ug/dL). Patients did not start new treatment for their anemia, including initiating new treatments for malignancy 3 months preceding, and within the data collection period. Patients were supplemented with Zinc Sulfate 50 mg daily and their HGB was followed over 12 months. A retrospective analysis was completed for prior medical history, lab data, and hemoglobin was tabulated at the time markers of 1, 3, 6, and 12 months following initiation of zinc supplementation. ANOVA, Wilcoxon rank-sum, and unpaired Students and t tests were performed to determine significant differences. p &amp;lt;0.05 is considered statistically significant. Results Thirty-Four patients were identified to have CKD 3-5 with chronic anemia and zinc deficiency. They were found to have no statistically significant baseline characteristics, hematologic values at time of diagnosis, or micronutrient and hormonal etiologies for anemia. HGB prior to supplementation averaged 9.96 g/dL, WBC averaged 5.8, and PLTS averaged 149. Following supplementation HGB at 1 month average was 10.47 g/dL (p=0.19 n=30), at 3 months average of 10.49 (p=0.12 n=31), at 6 months average of 11.03 (p=0.011 n=27), at 1 year 10.93 (p=0.03, n=17). Primary endpoint of HGB resolution was found in 12 of the 34 patients (35%). Secondary endpoint of HGB improvement by at least 1.0 g/dL was reached in 27% of patients at 1 month, 32% of patients at 3 months, 59% of patients at 6 months and 64% of patients at 12 months. Conclusions: Zinc supplementation improved patients' anemia with resolution of anemia in 35% of patients with incremental improvement in HGB over a 1 year time frame. There was statistically significant improvement from baseline HGB at the 6 and 12 month time markers. Further study is warranted to determine the specific mechanism of zinc deficiency in anemia with chronic kidney disease, as well as clinical studies determining zinc supplementation doses, monitoring, and toxicity.

Hemoglobin Response to Zinc Supplementation in Patients with Zinc Deficiency and Chronic Anemia

Background: Zinc is a necessary micronutrient used as a catalyst, structural element, and regulatory ion in many metabolic processes including erythropoiesis. Chronic anemia has an estimated prevalence of 5.6% within the US according to NHANES. Iron deficiency is considered the most common nutritional deficiency leading to anemia, but other nutritional deficiencies have been implicated in anemia including deficiencies of Vitamin A, B12, B6, C, D, and E, folate, Riboflavin, Copper, and Zinc. While zinc fortification has been studied in developing countries and has been associated with a decrease in the overall prevalence of anemia within the pediatric and maternal populations, there have been no studies in adults with chronic anemic in the developed world. The mechanism of Zinc in erythropoiesis is likely multifactorial with zinc acting as a catalyst in alpha-aminolevulinic acid dehydratase enzyme in iron metabolism and heme synthesis. Zinc's incorporation in the structure of the growth factor independent 1B (Gfi-1B) Zinc finger protein and GATA-1 Zinc finger transcription factor, which functions as a regulator in erythroid cell growth by modulating gene expression specific to erythroid series including the SMAD pathways and TGF-β signaling. Zinc's interaction in signaling cascades such as the growth hormone and insulin-like growth factor-1 pathways also result in increased erythropoietin transcription and therefore increased erythropoiesis. In addition, zinc is regarded as an important erythroid differentiation factor. This descriptive, retrospective study describes zinc deficient patients with chronic anemia, who underwent zinc supplementation, and their changes in hemoglobin (HGB) over a 12-month period in an academic outpatient hematology center in California, United States of America. Objectives: Primary endpoints: determine the rate of anemia resolution over 12 months following supplementation of zinc in patients with zinc deficiency and chronic anemia. Secondary endpoints: determine if zinc supplementation in zinc deficient patients with chronic anemia will improve HGB by at least 1.0 g.dL by 1, 3, 6, and 12 month time points. Methods: Ninety Three patients with chronic anemia (HGB &amp;lt;12 for women, HGB &amp;lt;13 for men for &amp;gt;3 months) over the age of 18 were identified to have zinc deficiency (plasma zinc concentration &amp;lt;65 ug/dL) in an academic outpatient hematology center in California. Patients did not start new treatment for their anemia, including initiating new treatments for malignancy 3 months preceding, and within the data collection period. Patients were supplemented with Zinc Sulfate 50 mg daily and their HGB was followed over 12 months. A retrospective analysis was completed for prior medical history, lab data, and HGB was tabulated at the time markers of 1, 3, 6, and 12 months following initiation of zinc supplementation. ANOVA, Wilcoxon rank-sum, and unpaired Students and t tests were performed to determine significant differences where p &amp;lt;0.05 is considered statistically significant. Results Prior to supplementation, average HGB among patients was 9.83 g/dL, WBC was 6.8 g/dL, MCV was 89 fl, PLTS were 211 g/dL. Following 1 month of supplementation average HGB was 10.46 g/dL (p = 0.015, n = 82), at 3 months average HGB was 10.75 g/dL (p = 0.0002, n = 83), at 6 months average HGB was 11.34 g/dL (p= 0.000000004, n = 74), and at 12 months average HGB was 11.48 g/dL (p = 0.00000002, n= 57). Primary endpoint of anemia resolution was found in 39 of 93 patients (42%). Secondary endpoint of HGB improvement by at least 1.0 g/dL was reached in 31% of patients at 1 month, 36% of patients at 3 months, 58% of patients at 6 months and 68% of patients at 12 months. Conclusions: Zinc supplementation significantly improved HGB levels in patients with zinc deficiency and chronic anemia, with resolution of anemia in 42% of patients. There was statistically significant improvement from baseline HGB at the1, 3, 6, and 12 month time markers. Further study is warranted to determine the specific mechanism of zinc deficiency in anemia, as well as clinical studies determining zinc supplementation doses, monitoring, and toxicity.

Zinc As an Erythrocyte Stimulating Agent in Myelodysplastic Syndrome

Background: The anemia highly associated with myelodysplastic syndrome (MDS) has been linked to numerous transcriptional factor regulation abnormalities, specifically SMAD 2/3 upregulation that forms an inhibitory feedback loop to downregulate erythrocyte stimulation (ESA), which can have therapeutic implications. There is evidence that zinc contributes to erythropoiesis through multifactorial mechanisms involving regulation and transportation of necessary micronutrients including copper and iron. Zinc is involved in cell signaling pathways for erythropoiesis including acting as a cofactor in the SMAD 2/3 complex, TGF-β signaling, and incorporation of zinc into GATA-1 (Zinc finger transcription factor). The interaction with zinc in signaling cascades such as the growth hormone and insulin-like growth factor-1 pathways also result in increased erythropoietin transcription and therefore increased erythropoiesis. In addition, zinc is regarded as an important erythroid differentiation factor which progress maturation of erythrocytes. Due to the multifactorial role of zinc in erythropoiesis, including acting as a cofactor in the SMAD 2/3 complex, it may represent an inexpensive, and well tolerated ESA or additional micronutrient to test and supplement in MDS. This descriptive, retrospective study describes zinc deficient patients with MDS, who underwent zinc supplementation, and their changes in hemoglobin (HGB) over a 12-month period in an academic outpatient hematology center in California, United States of America. Objectives: Primary endpoints: determine if zinc supplementation in zinc deficient MDS patients will improve HGB by at least 1.0 g.dL by 1, 3, 6, and 12 month time points. Methods: Eight adult patients with MDS were identified to have zinc deficiency (plasma zinc concentration &amp;lt;65 ug/dL). Patients were not started on ESAs or their treatments were not changed for the management of their MDS. Patients were supplemented with Zinc Sulfate 50 mg daily and their HGB was followed over 12 months. A retrospective analysis for medical history and lab data at time of zinc deficiency diagnosis and at 1, 3, 6 and 12 month following initiation of zinc supplementation was completed. ANOVA, Wilcoxon rank-sum, and unpaired Students and t tests were performed to determine significant differences where p &amp;lt;0.05 is considered statistically significant. Results: Prior to supplementation, average HGB among patients was 8.01 g/dL, WBC was 3.65 g/dL, MCV was 97.6 fl, PLTS were 140g/dL. Following 1 month of supplementation average HGB was 8.5 g/dL (p = 0.5, n = 7), at 3 months average HGB was 9.27 g/dL (p = 0.087, n = 7), at 6 months average HGB was 10.3 g/dL (p= 0.006, n = 7), and at 12 months average HGB was 10.28 g/dL (p = 0.04, n= 7). Primary endpoint of HGB improvement by at least 1.0 g/dL was reached in 29% of patients at 1 month, 43% of patients at 3 months, 86% of patients at 6 months and 71% of patients at 12 months. Resolution of anemia was reached in 1 patient (12.5%) of patients within 12 months. Conclusions: Zinc supplementation improved anemia in MDS patients with incremental improvement in HGB over a 1 year time frame. There was statistically significant improvement from baseline HGB at the 3, 6, and 12 month time markers. Further study is warranted to determine the specific mechanism of zinc deficiency in MDS and its mechanism as an erythrocyte stimulating agent as well as further study in non-zinc deficient patients, various zinc supplementation doses, monitoring, and toxicity.

The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.

Zinc is a structural component of proteins, functions as a catalytic co-factor in DNA synthesis and transcription of hundreds of enzymes, and has a regulatory role in protein-DNA interactions of zinc-finger proteins. For many years, zinc has been acknowledged for its anti-oxidative and anti-inflammatory functions. Furthermore, zinc is a potent inhibitor of caspases-3, -7, and -8, modulating the caspase-controlled apoptosis and necroptosis. In recent years, the immunomodulatory role of zinc in sepsis and COVID-19 has been investigated. Both sepsis and COVID-19 are related to various regulated cell death (RCD) pathways, including apoptosis and necroptosis. Lack of zinc may have a negative effect on many immune functions, such as oxidative burst, cytokine production, chemotaxis, degranulation, phagocytosis, and RCD. While plasma zinc concentrations decline swiftly during both sepsis and COVID-19, this reduction is primarily attributed to a redistribution process associated with the inflammatory response. In this response, hepatic metallothionein production increases in reaction to cytokine release, which is linked to inflammation, and this protein effectively captures and stores zinc in the liver. Multiple regulatory mechanisms come into play, influencing the uptake of zinc, the binding of zinc to blood albumin and red blood cells, as well as the buffering and modulation of cytosolic zinc levels. Decreased zinc levels are associated with increasing severity of organ dysfunction, prolonged hospital stay and increased mortality in septic and COVID-19 patients. Results of recent studies focusing on these topics are summarized and discussed in this narrative review. Existing evidence currently does not support pharmacological zinc supplementation in patients with sepsis or COVID-19. Complementation and repletion should follow current guidelines for micronutrients in critically ill patients. Further research investigating the pharmacological mechanism of zinc in programmed cell death caused by invasive infections and its therapeutic potential in sepsis and COVID-19 could be worthwhile.

Early supplementation with zinc proteinate does not change rectal microbiota but increases growth performance by improving antioxidant capacity and plasma zinc concentration in preweaned dairy calves.

The present study evaluated the effects of early supplementation with zinc proteinate (ZnP) or zinc oxide (ZnO) for 2 weeks on the growth performance, redox status, plasma trace element concentrations, and rectal microbiota of preweaned dairy calves. A total of 60 newborn healthy female Holstein dairy calves, with initial body weight (BW): 41.33 ± 0.62 kg, were randomly allocated to 5 groups of 12 each: a control group (CON); three groups supplemented with 261 (L-ZnP), 523 (M-ZnP), and 784 (H-ZnP) mg/day ZnP, equivalent to 40, 80, and 120 mg/day zinc, respectively; and one group supplemented with 232 mg/day ZnO, equivalent to 180 mg/day zinc (ZnO). Zinc supplements were administered on days 1-14, and the calves were followed up until day 70. Zinc supplementation increased total dry matter intake (DMI) and starter DMI compared with the CON group (p < 0.01). The final BW, average daily gain, and feed efficiency were higher in the M-ZnP, H-ZnP, and ZnO groups (p < 0.05). The incidence of diarrhea on days 1-28 was reduced by zinc administration (p < 0.01), whereas the incidence on days 29-56 was lower in the M-ZnP and ZnO groups (p < 0.05). Serum glutathione peroxidase activity, total antioxidant capacity, immunoglobulin G and plasma zinc concentrations were increased linearly (p < 0.05), while the serum concentration of malondialdehyde was decreased linearly (p < 0.01), as the dose of ZnP increased. ZnP yielding 80 mg/day zinc had similar effects as ZnO yielding 180 mg/day zinc, except that final BW was higher in the ZnO group (p < 0.05). At the phylum level, ZnO decreased the relative abundance of Firmicutes while increasing the abundance of Bacteroidetes (p < 0.05). At the genus level, ZnO increased the relative abundances of Prevotella, Subdoligranulum, and Odoribacter (p < 0.05). These findings indicated that early supplementation with ZnP did not affect the rectal microbiota of preweaned dairy calves but increased their growth performance, antioxidant capacity, and plasma zinc concentration. In summary, ZnP is an organic zinc source with greater bioavailability than ZnO for preweaned dairy calves. Early dietary supplementation with ZnP yielding 80 mg/day zinc is recommended.

Four-week administration of an energy and protein dense oral nutritional supplement improves micronutrient concentrations but does not completely correct deficiencies in institutionalized malnourished older adults.

Poor food intake is common among elderly living in nursing homes, leading to micronutrient deficiency (MD). There are no recommendations for the management of MD in malnourished older adults. We conducted a single arm, open-label, multicenter interventional study in institutionalized malnourished older adults to describe the effect of a 4-week daily energy and protein dense oral nutritional supplementation (ONS, 600 kcal, 30 g protein per unit) containing 50% of the recommended daily micronutrient intake on micronutrient status. Plasma concentrations of vitamins (A, B9, B12, C, E), magnesium (Mg), selenium (Se) and zinc (Zn), and erythrocyte vitamin B9 were measured at baseline and after 4 weeks. Forty-six participants completed the study (age 87.4 ± 6.6). At baseline, the most frequent MD were Se (48%), Zn (35%), Mg (24%) and vitamin C (24%). Plasma concentrations of vitamins B9, B12, C and E, Mg, Se and Zn significantly increased and the proportion of subjects with at least one MD decreased (p = 0.006). However, after 4 weeks, 40% of subjects still had at least one MD. ONS consumption improved micronutrient status but did not correct MD in all participants. Our data suggest that the prescription of vitamin, mineral and trace element supplementation should be considered in institutionalized malnourished older adults in addition to high energy and high protein ONS.

Cross-sectional observational study: Investigation of zinc concentration in white patients with cancer

ObjectivesNumerous studies describe the role of zinc in the immune system and metabolism. Zinc may influence the pathogenesis and prognosis of cancer. The aim of this study to determine the prevalence of zinc deficiency in patients with cancer. The study's primary objective was to evaluate the frequency of zinc deficiency in White patients with cancer and characterize the clinical factors predisposing individuals to decreased zinc concentration. The study also aimed to estimate the dose of zinc supplementation that would prevent deficiency. MethodsRetrospective data for this cross-sectional study were analyzed from 300 consecutive white patients diagnosed with neoplastic disease and admitted to a major oncology hospital for treatment. Zinc plasma concentration, nutritional status, body composition, and medical history of ailments and dysphagia were recorded. Supplementation was introduced in patients with zinc deficiency according to the local protocol. Zinc plasma levels were collected at follow-up visits. ResultsZinc deficiency was diagnosed in 68% of the patients. Poor nutritional status was significantly associated with zinc deficiency (low body mass index, weight loss, low albumin level). Low lean body mass (P = 0.003) and adipose tissue (P = 0.045) correlated with zinc deficiency. Patients with zinc deficiency reported dysphagia more frequently than those with normal zinc levels (18 versus 8%; P = 0.03). Squamous cell carcinoma was significantly associated with zinc deficiency (P = 0.043). Oral zinc supplementation resulted in reaching laboratory norms for plasma concentration in only 27% of patients with zinc deficiency and was not dependent on lower (10–15 mg) or higher (25–30 mg) dosing (P > 0.05). ConclusionsZinc deficiency is common in cachectic, malnourished patients with cancer. Nutritional guidelines for these patients should include screening for micronutrient deficiencies. Further studies are needed to determine the role, dosage, duration, and form of nutritional supplementation recommended for specific cancer diagnoses.

Imbalance of Plasma Copper and Zinc Levels and the Association Between the Cu/Zn Ratio and Lipid Peroxidation in Algerian Bipolar Patients.

Trace elements, through their interaction with biomolecules, can play an important role in the pathophysiology of bipolar disorder and protect against oxidative stress effects. The purpose of this study is to examine plasma concentration levels of zinc (Zn) and copper (Cu) of Algerian patients, diagnosed with bipolar disorder, and to compare these levels with those of healthy controls. The Cu/Zn ratio was calculated to explore a possible correlation between these elements and lipid peroxidation in the study groups. A total of 33 patients diagnosed with bipolar disorder and 38 healthy subjects participated in this study. Plasma copper and zinc concentrations were measured using a polarographic analyzer. The marker of plasma lipid peroxidation (Malondialdehyde:MDA) was determined by UV spectrophotometry. Plasma Cu concentrations were higher in patients compared to controls (p < 0.05), while the Zn level was significantly lower. Consequently, the Cu/Zn ratio was significantly different between patients and controls. Regarding MDA, no significant difference was noticed between the two study groups. However, in patients, a negative correlation was found between MDA and Cu/Zn ratio (r= -0.38, p= 0.027). These results suggested that an elevated Cu/Zn ratio is associated with attenuated lipid peroxidation in our bipolar patients.

Pre-analytical variables influence zinc measurement in blood samples.

Zinc deficiency continues to be a major concern for global public health. The zinc status of a target population is typically estimated by measuring circulating zinc levels, but the sampling procedures are not standardized and thus may result in analytical discrepancies. To examine this, we designed a study that controlled most of the technical parameters in order to focus on five pre-analytical variables reported to influence the measurement of zinc in blood samples, including (1) blood draw site (capillary or venous), (2) blood sample matrix (plasma or serum), (3) blood collection tube manufacturer (Becton, Dickinson and Company or Sarstedt AG & Co), (4) blood processing time (0, 4, or 24 hours), and (5) blood holding temperatures (4°C, 20°C, or 37°C). A diverse cohort of 60 healthy adults were recruited to provide sequential capillary and venous blood samples, which were carefully processed under a single chain of custody and measured for zinc content using inductively coupled plasma optical emission spectrometry. When comparing blood draw sites, the mean zinc content of capillary samples was 0.054 mg/L (8%; p<0.0001) higher than venous blood from the same donors. When comparing blood sample matrices, the mean zinc content of serum samples was 0.029 mg/L (5%; p<0.0001) higher than plasma samples from the same donors. When comparing blood collection tube manufacturer, the mean zinc content from venous blood samples did not differ between venders, but the mean zinc content from BD capillary plasma was 0.036 mg/L (6%; p<0.0001) higher than Sarstedt capillary plasma from the same donors. When comparing processing times, the mean zinc content of plasma and serum samples was 5-12% higher (p<0.0001) in samples processed 4-24 hour after collection. When comparing holding temperatures, the mean zinc content of plasma and serum samples was 0.5-7% higher (p = 0.0007 or p = 0.0061, respectively) in samples temporarily held at 20°C or 37°C after collection. Thus even with the same donors and blood draws, significant differences in zinc content were observed with different draw sites, tube types, and processing procedures, demonstrating that key pre-analytic variables can have an impact on zinc measurement, and subsequent classification of zinc status. Minimizing these pre-analytical variables is important for generating best practice guidelines for assessment of zinc status.