Zinc Deficiency with Poly-Micronutrient Deficiencies and Their Effects on Chronic Anemia before and after Micronutrient Replacement
Authors: Hagele Adam , Hanson Zachary D , Borecky Michael , Fay Andrew , Mirshahidi Saied , Akhtari Mojtaba 
Published: December 2024

Background:
Zinc (Zn) is an essential micronutrient in erythropoiesis where Zn deficiency has been shown to be a reversible cause of anemia. Zn is involved in multiple processes including iron metabolism, heme synthesis, erythroid cell growth regulation, and erythropoietin signaling. Poor dietary intake and decreased absorption may lead to Zn and other micronutrient deficiencies including iron, copper, vitamin B12, folate, manganese, and selenium which are implicated in anemia. While NHANES has studied populations at risk for micronutrient deficiencies, there has not been a study characterizing concurrent micronutrient deficiencies and their relationship with anemia.
This descriptive, retrospective study examined 75 patients with chronic anemia and concurrent nutritional deficiencies with Zn and iron, copper, B12, folate, manganese, and/or selenium. All patients were administered oral Zn replacement and changes in hemoglobin (HGB) were monitored over 12 months. This study was completed at an academic outpatient hematology center in Southern California.
Objective:
Describe patients with poly-micronutrient deficiencies and chronic anemia and the changes in hemoglobin after micronutrient replacement including rates of anemia resolution after micronutrient replacement.
Methods:
Seventy-five patients with chronic anemia (HGB &lt;12 g/dL for women, HGB &lt;13 g/dL for men for &gt;3 months) over the age of 18 were identified to have Zn deficiency (plasma zinc concentration, pZc, &lt;65 ug/dL) and at least one other micronutrient deficiency at time of Zn deficiency diagnosis, including iron (ferritin &lt;45 ng/mL and transferrin saturation &lt;20%), copper (serum copper level &lt;85 mcg/dL), B12 (serum B12 &lt;400 pg/mL and methylmalonic acid &gt;0.4 umol/L), manganese (serum manganese &lt;0.5 ug/dL), selenium (serum selenium &lt;110 ug/dL), and folate (serum folate &lt;3.4 ug/dL). Patients were also included if they had been on micronutrient replacement for iron deficiency, B12 deficiency, or folate deficiency within 3 months of Zn deficiency diagnosis. Oral Zn sulfate 220 (50)mg replacement as well as replacement of other deficient micronutrients were prescribed during the data collection period.
A retrospective analysis was completed for prior medical history, lab data; where HGB and pZc was tabulated at the time markers of 1, 3, 6, and 12 months following initiation of micronutrient replacement. Collected data was analyzed with ANOVA and CHI-squared for response in all patients.
Results
Seventy-five patients were found to have poly-micronutrient deficiencies, 19 of 64 tested patients were identified to have iron deficiency and were on oral (n = 35) or IV iron (n = 12). Thirteen of 63 patients were found to have copper deficiency, 7 of 34 patients were found to have B12 deficiency. No folate deficiency was identified in 36 tested patients. Manganese deficiency was found in 6 of 12 tested patients. Selenium deficiency was found in 7 of 24 tested patients. Folate supplementation was ongoing in 6 patients prior Zn deficiency diagnosis. Overall, 28 patients were found to have two micronutrient deficiencies, 6 patients were found to have three deficiencies, and one patient had four micronutrient deficiencies.
Prior to replacement, mean HGB among patients was 9.7 g/dL, WBC was 7.2 x103/uL, MCV was 89.5 fl, PLTS were 232 x103/uL, with pZc 52.1 ug/dL. Following 1 month of replacement, the mean HGB was 10.3 g/dL (p = 0.039, n = 60) with pZc 69.0 ug/dL (p = 4.8x10-8). The 3-month mean HGB was 10.79 g/dL (p = 0.00012, n = 64) with pZc 69.4 ug/dL (p = 2.2x10-11). The 6-month mean HGB was 11.5 g/dL (p= 5.9x10-9, n = 59), with pZc 75.0 ug/dL (p = 4.8x10-8). The 12-month mean HGB was 11.6 g/dL (p = 9.5x10-9, n= 49) with pZc of 68.1 ug/dL (p=1.8x10-5).
Anemia resolution was found in 38 of 75 patients (51%).
Conclusions:
Poly-micronutrient deficiencies were relatively common at the time of Zn deficiency diagnosis, where Zn deficiency was found with B12, iron, copper, selenium, and/or manganese deficiency. Patients who started micronutrient replacement were found to significantly improve HGB levels with resolution of anemia in 51% of patients. There was statistical significant improvement in HGB from baseline at the 1, 3, 6, and 12-month time markers. Further prospective studies are warranted to determine the specific relationship between mechanisms of Zn deficiency in anemia, as well as determining Zn replacement dosing, monitoring, and toxicities.